4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-ones

ABSTRACT

Compounds of the following formula   &lt;IMAGE&gt;   are useful as central nervous system depressants, tranquilizers, sedatives, growth promotors, anti-convulsants and muscle relaxants in mammalian species.

This is a division of application Ser. No. 778,823, filed Mar. 17, 1977,now U.S. Pat. No. 4,133,809, which is a division of application Ser. No.365,012 as filed May 29, 1973, now abandoned.

OBJECTS OF THE INVENTION

It is an object of the present invention to provide new compounds whichare useful as central nervous system depressants tranquilizers andsedatives. Another object is to provide methods for the preparation ofthese compounds. Another object is to provide compositions for theadministration of the compounds of the invention. These and otherobjects of the present invention will be apparent from the followingdescription.

SUMMARY OF THE INVENTION

It has now been found that4H-s-triazolo[4,3-a]-[1,5]benzodiazepin-5-ones of the following formula##STR2## are useful CNS depressants, tranquilizers, sedatives, growthpromotors, anti-convulsants and muscle relaxants in mammalian species.

DETAILED DESCRIPTION

The novel 4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-ones of formula 1 areuseful CNS depressants, tranquilizers and sedatives. The novel compoundsof formulas 3-12, and the compounds of formulas 13 and 14 some of whichare also novel, are intermediates for the compounds of formula 1.##STR3## In the foregoing formulas

R¹ is H; phenyl; X-substituted phenyl wherein X is as defined below; 2-,3- or 4-pyridyl, cycloalkyl of 3-5 carbons, alkyl of 1-4 carbonsoptionally substituted by amino, by monoalkylamino of 1-4 carbons, bydi-alkylamino of 1-4 carbons, by nitro, by cyano, by hydroxy, by alkoxyof 1-4 carbons, by alkanoyloxy of 1-4 carbons, by phenyl wherein thephenyl ring is optionally substituted by one or more X groups wherein Xis as defined below, or by a cyclic imine of formula ##STR4## where D ismethylene, oxygen or N-R¹⁰ and where p and q may be the same ordifferent and are the integers 1, 2, and 3 provided that p+q is at least1;

R² is H; alkyl of 1-4 carbons optionally substituted by amino,mono-lower alkyl, di-lower alkyl amino, cyclic imines of formula##STR5## where the cyclic imine is as defined above; hydroxy; alkoxy of1-6 carbons or ##STR6## where ##STR7## is an acyl group capable ofremoval and replacement by hydrogen or alkyl of 1-4 carbons and R⁵ isalkyl of 1-5 carbons optionally substituted by phenyl or X-substitutedphenyl; or R⁵ is phenyl optionally substituted by 1 or moreX-substituents

X and Y can be the same or different and are hydrogen, F, Cl, Br,trifluomethyl, alkyl of from 1-6 carbons, alkoxy of from 1-6 carbons,nitro, cyano, amino, alkanoylamino of 1-4 carbons, alkylthio of 1-6carbons, alkylsulfinyl of 1-6 carbons or alkyl sulfonyl of 1-6 carbons;

R³ is alkyl of from 1-6 carbons, benzyl or phenethyl;

R⁴ is t-butyl or benzyl optionally substituted on the phenyl ring by oneto three X groups;

R⁸ is alkyl of from 1-6 carbons, or phenyl optionally substituted by analkyl, aralkyl or aryl radical compatible with cyclization to form a7-membered ring;

R⁹ is hydrogen or alkyl of from 1-4 carbons;

n is 0, 1 or 2; m is 0 or 1;

R¹⁰ is hydrogen, alkyl of 1-4 carbons or phenyl optionally substitutedby X;

T is halogen, preferably chlorine, bromine or iodine.

R¹¹ is hydrogen or alkyl of 1-4 carbons;

R¹² is alkyl of 1-4 carbons substituted by the groups ##STR8## where Pand Q may be the same or different and may be hydrogen, phenyl,X-substituted phenyl, naphthyl or X-substituted naphthyl, with theproviso that at least one of P and Q is one of the foregoing arylradicals,

R¹³ is alkyl of 1-6 carbons.

Preferably, R¹ is hydrogen, cycloalkyl of 3-5 carbons, or alkyl of 1-4carbons optionally substituted by amino, nitro, cyano, hydroxy, alkoxyof 1-4 carbons, alkanoyloxy of 1-4 carbons, mono-alkylamino of 1-4carbons, dialkylamino of 1-4 carbons or by a cyclic imine of formula##STR9## where D, p and q are as previously defined. Most preferably, R¹is hydrogen or alkyl of 1-4 carbons.

Preferably, R² is hydrogen, alkyl of 1-4 carbons or hydroxy.

Preferably, R⁸ is alkyl of 1-4 carbons. The radical R⁸ as well as theoxygen atom to which it is bonded are removed during cyclization.

SYNTHESIS

The 4-H-s-triazolo[4,3-a][1,5]benzodiazepin-5-ones of formulas 1 and 11can be prepared by several methods.

One method (hereinafter called the first method) involves reacting acompound of formulas 3-6 with from about 0.8 to about 6.0, preferablyfrom about 1.0 to about 3.0 molar equivalents of an acid hydrazide offormula ##STR10## (where R¹ is as defined previously) in an inert,organic solvent or mixture of solvents. Typical organic solvents whichmay be used in the above reaction include aryl hydrocarbons, e.g.,benzene, toluene, xylene and the like; chlorinated hydrocarbons such asdi-, tri-, tetra-chloroethanes and the like; lower molecular weightalkanols of 1-6 carbons such as methanol, ethanol, tertiary butylalcohol, n-butanol and the like; N,N-dialkylformamides, N,N-dialkylalkanoyl amides wherein the alkyl and alkanoyl radicals have 1-4carbons, such as dimethylformamide, dimethylacetamide and the like;hexamethylphosphorous triamide, ethers, such as dioxane and the like anddi-lower alkyl sulfoxides, such as dimethyl sulfoxide and the like. Thereaction is carried out at from about 40° C. to about 250° C.,preferably from about 60° C. to about 180° C., until a significantamount of end product is obtained, typically, for from about 1/4 toabout 92 hours, preferably from about 1 to about 48 hours.

The final product of formula 1 or 11 is isolated by conventionaltechniques. For example, the reaction mixture is evaporated and theresidue is partitioned between aqueous sodium bicarbonate and awater-immiscible inert, organic solvent, such as halogenatedhydrocarbons, e.g., methylene chloride, chloroform or trichloroethylene;alkyl esters wherein both the acid and alcohol from which the ester isderived may have from 1 to 4 carbon atoms, e.g., ethyl acetate, propylacetate, ethyl propionate and the like. The organic solvent is washedwith water, dried and chromatographed.

A compound of formula 12 may be converted to the corresponding compoundof formula 1 by another method for the synthesis of compounds of formula1 where R¹ is alkyl substituted by amino, mono-alkyl amino or a hydroxygroup. Such a method involves reacting a compound of formula 12 withappropriate reagents under appropriate conditions as described belowsuitable for the selective replacement of the ##STR11## hydrogen atom.

One such method involves reacting the compounds of formula 12 with atleast about 0.5 preferably at least about 0.8, molar equivalent of aninorganic hydrogen halide (preferably hydrogen chloride, hydrogenbromide and hydrogen fluoride) or with a halogenated lower alkylcarboxylic acid (preferably trifluoroacetic acid). The reaction is runin anhydrous hydrogen fluoride, or, when employing other acids, in anoptional inert solvent.

Typical solvents include lower carboxylic acid such as acetic acid andthe like; ethers such as diethyl ether, dioxane, tetrahydrofuran and thelike; lower molecular weight alkanols of 1-6 carbons such as methanol,ethanol, and the like; alkyl esters wherein both the acid and thealcohol from which the ester is derived may have from 1-4 carbon atomssuch as ethyl acetate, propyl acetate, ethyl propionate and the like;halogenated hydrocarbons such as methylene chloride, chloroform, di-,tri- and tetrachloroethanes and the like; nitroalkanes of 1-4 carbonssuch as nitromethane, nitroethane and the like; or lower alkyl ketonesof 2-5 carbons such as acetone, methylethyl ketone and the like.

The reaction is carried out at from about -50° C. to about 200° C.,preferably from about 0° C. to about 120° C., until a significant amountof end product is obtained, typically, for from about 1/10 to about 92,preferably from about 1/6 to about 30 hours. The corresponding productof formula 1 is isolated by conventional techniques. For example, withall acids except hydrogen fluoride, the reaction mixture is diluted withan inert water-immiscible organic solvent, washed with dilute aqueoussodium bicarbonate, dried and chromatographed. When using hydrogenfluoride, the hydrogen fluoride is evaporated, the residue dissolved inan inert organic solvent, such as halogenated hydrocarbons, e.g.,methylene chloride, chloroform or trichloroethylene; alkyl esterswherein both the acid and the alcohol from which the ester is derivedmay have from 1-4 carbon atoms, e.g., ethylacetate, propyl acetate,ethyl propionate and the like, washed with water, dried andchromatographed.

Another such method for the selective replacement of the ##STR12## groupby hydrogen in compounds of formula 12 involves the reaction of saidcompounds of formula 12 with hydrogen in the presence of an appropriatecatalyst, in an inert organic solvent. Typical catalysts includeplatinum, Raney nickel and, preferably, palladium. Typical solventsinclude lower alkanols of 1-6 carbons such as ethanol, methanol, and thelike; formic acid; lower alkanoic acids of 2-5 carbons such as aceticacid and the like as well as other typical solvents well known to thoseversed in the art. Typical hydrogenation pressures are from about 0.1 toabout 2000 atmospheres, preferably from about 0.8 to about 100atmospheres. The reactions are carried out for from about 1/2 to about96 hours, preferably from about 1 to about 72 hours at from about 0° C.to about 200° C., preferably from about 20° C. to about 120° C. Theproducts are isolated in a conventional manner. For example the catalystis filtered off, the solvent evaporated and the product chromatographed.

Another method for the synthesis of compounds of formulas 1 and 11involves heating compounds of formula 7 either alone or in an inert,organic solvent at from about 60° C. to about 350° C., preferably fromabout 80° C. to about 300° C. for from about 1/2 to about 72 hours,preferably from about 1 to about 24 hours. Typical inert, organicsolvents that are used are those defined in the first method. Theproducts are isolated by conventional techniques. For example, thereaction is diluted with a water-immersible inert, organic solvent,washed with water dried and chromatographed.

Another method (hereinafter called the fifth method) of synthesis forcompounds of formulas 1 and 11 involves reacting compounds of formula 8with from about 0.8 to about 6, preferably from about 1 to about 3,molar equivalents of acyl derivatives of formula ##STR13## (where W islower alkoxy, halogen, hydroxy or ##STR14## in an optional inert organicsolvent. Typical inert organic solvents which may be used include arylhydrocarbons such as benzene, toluene, xylene and the like; chlorinatedhydrocarbons such as tri- and tetrachloroethanes and the like; etherssuch as 1,2-dimethoxyethane, tetrahydrofuran, dioxane and the like;N,N-dialkylformamides and alkyl alkanoylamides wherein the alkyl andalkanoyl radicals have 1-4 carbons such as dimethylformamide,dimethylacetamide and the like. Where W is lower alkoxy or hydroxy,suitable solvents also include lower alkanols of 1-6 carbons such asethanol, t-butyl alcohol and n-butyl alcohol and the like and dimethylsulfoxide. The reaction conditions and the isolation of the products areas described in the first method.

Another method for the synthesis of compounds of formulas 1 and 11involves reacting compounds of formula 9 with at least about 0.1preferably from at least about 0.8 to about 3 molar equivalents of anacyl derivative of formula ##STR15## in the presence of at least about0.1, preferably from at least about 0.8 to about 3, molar equivalents ofan inorganic hydrohalic acid, preferably hydrogen bromide or hydrogenchloride. The reaction can optionally be run in an inert organicsolvent. Where compounds of formula ##STR16## are "strong" carboxylicacids, such as chloroacetic, trifluoroacetic and oxalic acid and thelike, the use of a hydrohalic acid is optional. Typical inert organicsolvents include lower molecular weight ethers such as1,2-dimethoxyethane, dioxane, tetrahydrofuran and the like; halogenatedhydrocarbons such as methylene chloride, di-, -tri- andtetra-chloroethane and the like; nitroalkanes of 1-4 carbons such asnitromethane, nitroethane and the like; lower alkanols of 1-6 carbonssuch as ethanol, n-butanol and the like. The reaction is carried outfrom about -50° C. to about 250° C., preferably from about +10° to about180° C., for from about 1/4 to about 96 hours, preferably from about 1/2to about 48 hours. The products are isolated using conventionaltechniques as described in the first method.

Compounds of formula 1 where R² is lower acyloxy (of formula ##STR17##or lower alkoxy (of formula --OR¹³) can be prepared by reactingcompounds of formula 1, where R² is halogen, with the appropriate acidof formula ##STR18## (or alkali metal or tri-lower alkyl amine saltthereof) or with the appropriate alcohol of formula HOR¹³ (or alkalimetal salt thereof), respectively. The reaction is run in excess acid oralcohol, respectively, or, optionally, in an inert organic solvent suchas ethers such as dioxane, tetrahydrofuran, 1,2-dimethoxyethane and thelike; N,N-dialkylformamides, N,N-dialkylalkanoyl amides wherein alkyland alkanoyl radicals have 1-4 carbon atoms, such as dimethyl formamide,dimethylacetamide and the like. The reaction is carried out for fromabout 1/4 to about 72 hours, preferably about 1/2 to about 12 hours, atfrom about -20° C. to about 150° C., preferably about 20° C. to about100° C. The The products are isolated by conventional techniques asdescribed in the first method.

The compounds of formula 1 where R² ═OH are obtained by reactingcompounds of formula 1 where R² is ##STR19## with from about 0.2 toabout 6, preferably about 0.8 to about 3, molar equivalents of an alkalimetal (preferably sodium and potassium) hydroxide, bicarbonate orcarbonate in an inert organic solvent, in optional presence of water.Suitable organic solvents include lower molecular weight alcohols, suchas methanol, ethanol and the like; water-miscible ethers such astetrahydrofuran, 1,2-dimethoxyethane, dioxane and the like;N,N-dialkylformamides, N,N-dialkyl alkanoylamides wherein the alkyl andalkanoyl radicals have 1-4 carbons such as dimethylformamide,dimethylacetamide, and the like. The reaction is carried ot at fromabout -50° C. to about 100° C., preferably about -20° C. to about 70°C., for from about 1/4 to about 72 hours, preferably about 1/2 to about24 hours. The products are isolated in a conventional manner. Forexample, the reaction mixture is neutralized with acetic acid,evaporated and chromatographed.

The compounds of formula 1 where R² is halogen (preferably bromine orchlorine) are prepared by reacting compounds of formula 1 where R² ishydrogen with from about 0.5 to about 3, preferably from about 0.8 toabout 1.3, molar equivalents of a lower alkyl N-haloamide, lowercycloalkyl N-haloimide or aryl sulfonyl N-haloamide, in the presence ofa free radical catalyst, in an inert organic solvent. Suitable N-haloamides and imides include N-chloro and N-bromo-succinimide, and thelike; N-chloroacetamide and the like; and N-chlorobenzenesulfonamide andthe like. Suitable free radical catalysts include azobis-lower alkylnitriles such as the preferred catalyst, azebisisobutyronitrile;di-lower alkyl peroxides such as di-t-butylperoxide; di-acyl peroxidessuch as acetyl peroxide; per esters such as t-butylperbenzoate;hydroperoxides such as t-butyl-hydroperoxide and the like. Typical inertorganic solvents are aromatic hydrocarbons, such as benzene, toluene,xylene and the like; and chlorinated hydrocarbons such as methylenechloride, chlorobenzene, carbon tetrachloride, di-, tri- andtetrachloroethanes, chlorobenzene, and the like. The reaction is carriedout at from about 25° C. to about 200° C., preferably at about thereflux temperature of the reaction medium, for from about 1/4 to about24 hours, preferably for from about 1/2 to about 5 hours. The product isisolated by conventional techniques. For example, the reaction mixturecooled to room temperature and evaporated.

Compounds of formula 1 where R² is alkyl of 1-4 carbons substituted byamino are prepared by reacting compounds of formula 1 where R² ishydrogen with from about 0.5 to about 12, preferably from about 0.8 toabout 3.0 molar equivalents of an appropriate base, followed by reactionof the thus formed salt with a corresponding molar equivalent of anappropriate amino alkyl alkylating agent of formula R⁶ --M where R⁶ isthe amino alkyl moiety and M is halogen, preferably chlorine, bromine,iodine; ##STR20## or an alkyl or arylsulfonate of formula ##STR21##where R⁷ can be alkyl of 1-6 carbons or aryl of from about 6 to 10carbons optionally substituted by halogen, nitro or alkyl of 1-3carbons, or R⁶ --M may be any other agent (within the definition of R⁶)capable of introducing an aminoalkyl group. The reaction is run in anessentially inert organic solvent.

Typical bases include alkali metal (preferably sodium and potassium)salts as well as thallous salts of lower molecular weight alkanols of1-6 carbons such as methanol, ethanol, propanol, isopropal, t-butanol,amyl alcohol and the like; alkali metal (preferably sodium) hydrides;alkali metals (preferably sodium and potassium); alkali metal(preferably sodium and potassium) salts of acidic hydrocarbons such astriphenylmethane and the like as well as any other base known to thoseskilled in the art for generating salts of acidic methylene groups.Typical organic solvents include those described in the first method.

The reaction is carried out at from about -20° C. to about 300° C.,preferably from about 0° C. to about 100° C. for from about 0.2 hour toabout 96 hours, preferably from about 0.5 hour to about 72 hours.

The products of formula 1 where R² is alkylamino are isolated byconventional techniques. For example the reaction mixture is evaporated;the residue is diluted with a water-immiscible, inert solvent such asmethylene chloride, washed with water, dried and chromatographed.

Compounds of formula 1 can also be prepared by reacting compounds offormula 10 with at least from about 0.5 to a large excess, preferably atleast from about 0.8 to about 100, molar equivalents of an aryl halide,in the presence of a copper catalyst, in an appropriate solventcontaining from about 0.5 to about 1000, preferably about 0.8 to about100, molar equivalents of an appropriate hydrogen halide acceptor. Thepreferred aryl halides are those of formula AR--K where AR is phenyloptionally substituted by X and where K is preferably chlorine, bromineor iodine. The preferred copper catalysts are powdered copper metal,copper oxides and cuprous and cupric salts. Typical solvents includeN,N-dialkylformamides and N,N-dialkyl alkanoyl amides wherein the alkyland alkanoyl radicals have 1-4 carbons such as N,N-dimethylformamide,N,N-dimethylacetamide and the like; dialkyl sulfoxides of 2-6 carbonssuch as dimethyl sulfoxide and the like; and alkylphosphorous triamidesof 4-10 carbons such as hexamethylphosphorous triamide. Appropriatehydrogen halide acceptors include alkali metal (preferably sodium orpotassium) carbonates, bicarbonates, or lower alkyl carboxylic acidsalts thereof (e.g., acetates). The reaction is carried out at fromabout 50° C. to about 200° C., preferably at from about 90° C. to about180° C., for from about 1/4 to about 72 hours, preferably for from about1/2 to about 14 hours. The product is isolated in a conventional manner.For example, the reaction mixture is diluted with methylene chloride,washed with dilute aqueous ammonium hydroxide and chromatographed.

Compounds of formula 2 where m is one are prepared by reacting compoundsof formula 17 where m is one with from about 0.5 to about 10, preferablyabout 0.8 to about 2, molar equivalents of a malonyl dihalide(preferably malonyl dichloride or malonyl dibromide) or an alkyl malonicacid derivative (of formula ##STR22## where S is halogen or --OR¹³) inan inert organic solvent. Typical solvents are aromatic hydrocarbonssuch as benzene, toluene, xylene, and the like; certain ethers such asdioxane, 1,2-dimethoxyethane, tetrahydrofuran and the like; chlorinatedhydrocarbons such as di-, tri- and tetra-chloroethanes, chloroform,chlorobenzene, CCl₄, dichloroethane and the like; N,N-dialkylformamidesand N,N-dialkyl alkanoylamides wherein the alkyl and alkanoyl radicalshave 1-4 carbons such as N,N-dimethylformamide, N,N-dimethylacetamideand the like.

The reaction is carried out at from about -10° C. to about 200° C.,preferably at from about +10° C. to about 140° C., for from about 1/4 toabout 92 hours, preferably for from about 1 to about 24 hours. Theproducts are isolated in a conventional manner. For example, the solventis partially evaporated and the product filtered off.

Compounds of formula 2 where m is one are also prepared by reactingcompounds of formula 17 where m is one with from about 0.5 to about 3,preferably from about 0.8 to about 1.4, molar equivalents of a malonicacid of the formula ##STR23## in an aqueous mineral acid. Typicalmineral acids include sulfuric, hydrobromic and hydrochloric acid. Theconcentration of acid is from about 2 to about 7 normal, preferably fromabout 3.5 to about 4.5, normal. The reaction is carried out for fromabout 1/4 to about 92 hours, preferably for from about 1/2 to about 24hours at from about 40° C. to about 200° C., preferably from about 60°C. to about 140° C. The product is isolated in a conventional manner.For example, the reaction is cooled and the product filtered off.

Compounds of formula 2 where m is one are also prepared by reactingcompounds of formula 13 where m is one in the optional presence of acatalyst in the optional presence of water in an organic solvent.Typical catalysts include inorganic acids such as hydrogen chloride,hydrogen bromide and sulfuric acid as well as bases such as alkali metal(preferably sodium and potassium) hydroxides and lower alkoxides andother conventional bases used for the condensation of an aryl amine withan alkyl carboxylic acid ester. Typical solvents include alkanols of 1-6carbons such as methanol, ethanol and the like; certain water-miscibleethers such as tetrahydrofuran, dioxane and the like;N,N-dialkylformamides and N,N-dialkyl alkanoyl amides wherein the alkyland alkanoyl radicals have 1-4 carbons such as N,N-dimethyl formamide,dimethylacetamide and the like. The reaction is carried out for fromabout 1/2 to about 96 hours, preferably for from about 1 to about 24hours at from about -20° C. to about 150° C., preferably 0° C. to 100°C. The product is isolated in a conventional manner. For example thereaction is neutralized, diluted with a water-immiscible inert organicsolvent, washed with water, dried and chromatographed.

Compounds of formula 2 where m is one are also prepared by reactingcompounds of formula 14 where m is one with an appropriate reducingagent, in the presence of an acid or base catalyst, in the optionalpresence of water in an organic solvent. Typical reducing systemsinclude powdered iron, zinc and tin in the presence of an aqueous acid,in an optional organic solvent. Typical acids include hydrohalic acids(preferably hydrochloric acid) and alkyl carboxylic acids of 1-6 carbonatoms such as acetic acid and the like. Typical solvent systems includeaqueous alkanols of 1-6 carbons such as methanol, ethanol and the like.Still other reducing agents include stannous chloride and aqueoushydrochloric acid; sodium hydrosulfite; ferrous sulfate and ammoniumhydroxide; ammonium sulfide; hydrazine in the presence of palladizedcharcoal; sodium sulfide and ammonium chloride, sodium sulfide andsulfur. The reaction is carried out at from about 0° C. to about 200°C., preferably at from about 10° C. to about 140° C. for from about 1/6to about 92 hours, preferably for from about 1/2 to about 24 hours. Theproducts are isolated by conventional techniques. For example thereaction is filtered, evaporated, saponified in alcoholic potassiumhydroxide, evaporated, taken up in water, adjusted to pH 6 and theproduct filtered off and chromatographed.

Compounds of formula 2, where m is zero are prepared from compounds offormulas 13, 14 and 17 where m is zero by the methods described for thepreparation of compounds of formula 2, wherein m is one [see also:Chemical Reviews, 68, 780ff (1968) and references cited therein and, S.African Pat. No. 6800803 (1968)].

Compounds of formula 3 can be prepared by reacting compounds of formula2 with from about 0.5 to about 2.0, preferably with from about 0.9 toabout 1.2, molar equivalents of phosphorous pentasulfide in an aprotic,essentially inert organic solvent. Typical inert organic solventsinclude aryl hydrocarbons such as benzene, toluene or xylene; aliphatichydrocarbons of 5-12 carbons, such as hexane, heptane and the like;alicyclic hydrocarbons of 5-8 carbons, such as cyclohexane and the like;basic carbocyclic amines such as pyridine, quinoline, γ-picoline and thelike; and any other conventional solvent materials which are relativelyinert with regard to the starting materials.

The reaction is carried out at from about 10° C. to about 250° C.,preferably at from about 50° C. to about 150° C., for from about 5minutes to about 72 hours, preferably from about 10 minutes to about 6hours. The product of formula 3 is isolated by conventional techniques.For example the reaction solvent is evaporated, the residue stirred withice water, extracted into a water-immiscible organic solvent; thewater-immiscible solvent is washed consecutively with water, diluteaqueous hydrohalic acid, dried and chromatographed.

Compounds of formula 4 are prepared by reacting compounds of formula 3with from about 0.5 to about 6, preferably from about 0.8 to about 1.2,molar equivalents of an alkylating agent of formula R³ --M [where M maybe halogen, preferably bromine or iodine; ##STR24## or an alkyl orarylsulfonate moiety of formula ##STR25## where R⁷ can be alkyl of 1-6carbons or aryl of from 6 to 10 carbons optionally substituted byhalogen, nitro or alkyl of 1-3 carbons or R³ --M may be any other agent(within the definition of R³) capable of selectively alkylating thesulfur atom in the presence of the other groups in 3] in the presence ofan appropriate base in an inert organic solvent. Typical bases includealkali metal hydroxides (preferably sodium and potassium hydroxide),alkali metal carbonates (preferably sodium and potassium bicarbonate orcarbonate) and appropriate organic tertiary amines such astrialkylamines, e.g., triethylamine and the like, and pyridine and thelike. Typical solvents include lower molecular weight alkanols of 1-6carbons such as methanol, ethanol and the like; water-miscible etherssuch as dioxane, tetrahydrofuran, 1,2-dimethoxyethane and the like;N,N-dialkylformamides and N,N-dialkyl alkanoyl amides wherein the alkyland alkanoyl radicals have 1-4 carbons such as dimethyl formamide ordimethylacetamide and the like; alkyl ketones of 2-5 carbons such asacetone, methylethylketone and the like, and dimethyl sulfoxide. Thereaction is carried out at from about -60° C. to about 150° C.,preferably at from about 0° C. to about 90° C., for from about 1 minuteto about 90 hours, preferably for from about 5 minutes to about 24hours. The products of formula 4 are isolated by conventionaltechniques. For example, the reaction is diluted with water, extractedwith a water-immiscible solvent, dried and chromatographed.

Compounds of formula 5 can be prepared by reacting compounds of formula2 with from about 0.5 to about 3, preferably with from about 0.8 toabout 1.2, molar equivalents of a suitable halogenating agent in aninert organic solvent, in the optional presence of an acid protonacceptor. Typical halogenating agents include the phosphorous halidessuch as phosphorous pentachloride, phosphorous oxychloride, andphosphorous oxybromide. Typical inert organic solvents include aromatichydrocarbons such as benzene, toluene, xylene and the like; chlorinatedhydrocarbons such as methylene chloride, chloroform, chlorobenzene,CCl₄, di-, tri- and tetrachloroethanes and the like. Phosphorousoxyhalides such as phosphorous oxychloride and the like can be used bothas solvent and halogenating agent.

Optional acid proton acceptors include N,N-di-lower alkyl aryl aminessuch as N,N-dimethylaniline, N,N-diethylaniline and the like andtrialkylamines such as triethylamine, tributylamine and the like.

The reaction is carried out at from about 0° C. to about 200° C.,preferably at from about 40° C. to about 150° C., for from about 1/4 toabout 72 hours, preferably for from 1/2 to about 24 hours. The productsof formula 5 are isolated by conventional techniques. For example, thereaction mixture is evaporated and the residue is diluted with anaprotic, inert, organic solvent, washed with cold water, and thenevaporated. The residual product is stirred with a non-solubilizinginert organic solvent, such as carbon tetrachloride, and the product isfiltered off.

Compounds of formula 6 are prepared by reacting compounds of formula 2with from about 0.8 to about 50, preferably about 1 to about 20, molarequivalents of a diazo-lower alkane in an inert organic solvent. Typicalinert organic solvents include lower molecular weight ethers such asdiethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and thelike; alkanols of 1-6 carbons such as methanol, ethanol and the like andhalogenated hydrocarbons such as chloroform methylene chloride, CCl₄,1,2-dichloroethane, chlorobenzene, di-, tri- and tetrachloroethanes andthe like.

The reaction is carried out at from about -50° C. to about 100° C.,preferably at from about 0° C. to about 60° C., for from about 1/4 hourto about 72 hours, preferably for from about 1/2 to about 12 hours.

The products of formula 6 are isolated by conventional techniques. Forexample, the reaction is filtered, evaporated and chromatographed.

Another method for the preparation of compounds of formula 6 involvesreacting compounds of formula 2 with from about 0.5 to about 3,preferably with from about 0.8 to about 1.4, molar equivalents of atri-lower alkyl oxonium fluoroborate in an inert organic solvent.Typical solvents include halogenated hydrocarbons such as methylenechloride, CCl₄, chloroform, 1,2-dichloroethane, chlorobenzene, di-, tri-and tetrachloroethanes and the like. The reaction is carried out at fromabout -50° C. to about 100° C., preferably at from about -20° C. toabout 70° C. for from about 1/2 hour to about 72 hours preferably forfrom about 1 to about 24 hours.

The products of formula 6 are isolated by conventional techniques. Forexample, the reaction mixture is washed with cold aqueous potassiumbicarbonate, dried and the solvent evaporated.

Compounds of formula 7 are prepared by reacting compounds of formulas3-6 with from about 0.8 to about 6.0, preferably with from about 1 toabout 3, molar equivalents of an acid hydrazide of formula ##STR26## inan inert organic solvent. Typical solvents include alkanols of 1-6carbons such as methanol, ethanol, t-butanol, n-butanol and the like;aromatic hydrocarbons such as benzene, toluene, xylene and the like;chlorinated hydrocarbons such as methylene chloride, chloroform, di-,tri- and tetrachloroethane and the like; ethers such as tetrahydrofuran,dioxane, 1,2-dimethoxyethane and the like; N,N-dialkylformamides,N,N-dialkyl alkanoyl amides wherein the alkyl and alkanoyl radicals havefrom 1-4 carbons, such as N,N-dimethyl formamide, N,N-dimethylacetamideand the like; hexamethylenephosphorous triamide and dimethyl sulfoxide.The reaction is carried out at from about -30° C. to about 160° C.preferably at from about 30° C. to about 120° C., for from about 1/2 toabout 96 hours, preferably for from about 2 to about 12 hours. Theproducts of formula 7 are isolated by conventional techniques. Forexample, the reaction is diluted with a water-immiscible inert organicsolvent, washed with water, dried and chromatographed.

Compounds of formula 8 are prepared by reacting compounds of formula 9with at least about 0.1 preferably from about 0.8 to about 3, molarequivalents of an inorganic hydrohalic acid, preferably hydrogen bromideor hydrogen chloride in an inert organic solvent. Typical inert organicsolvents include alkanols of 1-6 carbons such as ethanol, t-butanol andthe like; lower molecular weight ethers such as dioxane,tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane and the like;chlorinated hydrocarbons such as methylene chloride, CCl₄,chlorobenzene, di-, tri-, and tetrachloroethanes, chloroform and thelike; N,N-dialkylformamides, N,N-dialkyl alkanoyl amides wherein thealkyl and alkanoyl radicals have 1-4 carbons, such as dimethylformamide, dimethylacetamide and the like. The reaction is run for fromabout 1/4 to about 90 hours, preferably for from about 1/2 to about 3hours, at from about -50° C. to about 100° C., preferably at from about-30° C. to about 80° C. The products are isolated by conventionaltechniques. For example, the solvent is evaporated at room temperaturein vacuo, the residue stirred in cold water containing an alkali metalhydroxide, equivalent in molar amount to the amount of hydrohalic acidused, and the product is then removed by filtration and dried.

Compounds of formula 9 are prepared by reacting compounds of formulas3-6 with from about 0.5 to about 6, preferably with from about 0.8 toabout 3, molar equivalents of a compound of formula ##STR27## in aninert organic solvent. Typical solvents are those as defined in thefirst method. The reaction is carried out at from about 40° C. to about250° C., preferably at from about 50° C. to about 180° C. for from about1/4 hours to about 92 hours, preferably about 1 to about 48 hours. Theproducts of formula 9 are isolated by conventional techniques asdescribed in the first method.

Compounds of formula 10 are prepared by the removal of the N⁶ benzylgroup in compounds of formula 11 wherein the benzyl group is replaced byhydrogen. Suitable reagents and conditions are those described below forthe debenzylation of compounds of formula 12. The isolation of theproducts is as exemplified for compounds of formula 12.

Compounds of formula 12 are prepared by reacting compounds of formulas3-6 wherein m is zero with from about 0.5 to about 6, preferably withfrom about 0.8 to about 3, molar equivalents of an acid hydrazide offormula ##STR28## in an inert organic solvent. Typical solvents, theconditions of the reaction and the isolation of the product are asdescribed in the first method.

Compounds of formula 13 are prepared by reacting compounds of formula 14with an appropriate reducing agent under selective conditions in aninert organic solvent.

Typical reducing agents include a metal catalyst, preferably Raneynickel, and hydrogen in the optional presence of a hydrogen halide in aninert organic solvent. Typical solvents include alkanols of 1-6 carbonssuch as methanol, ethanol and the like. The preferred optional hydrogenhalides are hydrogen chloride and hydrogen bromide. The reactions arecarried out for from about 1/6 hour to about 92 hours, preferably forfrom about 1/2 to about 24 hours at from about 0° C. to about 150° C.,preferably at from about 10° C. to about 120° C. Hydrogen pressures arefrom about 0.1 to about 100 atm. preferably about 0.8 to about 10 atm.The reaction is stopped after approximately three molar equivalents ofhydrogen have been absorbed. The products are isolated in a conventionalmanner. For example the reaction is filtered, made alkaline to pH 8,extracted with a water-miscible organic solvent, washed with water,dried and chromatographed.

Compounds of formula 14 are prepared by reacting compounds of formula 15with from about 0.5 to about 6, preferably with from about 0.8 to about2, molar equivalents of a compound of formula 16 (where B is halogen,preferably chlorine or bromine, or a group of formula ##STR29## in aninert organic solvent. Typical solvents include aromatic hydrocarbonssuch as benzene, toluene, xylene and the like; halogenated hydrocarbonssuch as chloroform, methylene chloride, CCl₄, chlorobenzene, di-, tri-and tetrachloroethane and the like; certain ethers such as1,2-dimethoxyethane, dioxane, tetrahydrofuran and the like;N,N-dialkylformamides, N,N-dialkyl alkanoyl amides wherein the alkyl andalkanoyl radicals have 1-4 carbons, such as N,N-dimethyl amide and thelike. The reactions are carried out for from about 1/2 to about 92hours, preferably for from about 2 to about 24 hours at from about -20°C. to about 150° C., preferably at from about +5° C. to about 100° C.The products are isolated by conventional techniques as examplified inthe first method.

Compounds of formula 17 are prepared by reacting compounds of formula 15with an appropriate reducing agent in an essentially inert organicsolvent. Typical reducing agents include a metal catalyst such aspalladium, platinum and the preferred catalyst Raney nickel in thepresence of hydrogen in the optional presence of a hydrogen halide(preferably hydrogen chloride and hydrogen bromide). Typical solventsinclude alkanols of 1 to 6 carbons such as methanol, ethanol, propanol,isopropanol and the like.

Hydrogen pressures are from about 0.1 to about 100 atm., preferably fromabout 0.8 to about 10 atm. The reaction is stopped after approximatelythree molar equivalents of hydrogen have been absorbed.

The reaction is carried out at from about 0° C. to to about 150° C.,preferably from about 20° C. to about 100° C. for from about 0.2 hour toabout 96 hours, preferably from about 0.5 hour to about 24 hours.

The products of formula 17 are isolated by conventional techniques. Forexample the reaction is filtered, made alkaline to pH 8, diluted with awater-immiscible, inert organic solvent, washed with water, dried andevaporated.

Compounds of formula 15 are prepared by reacting compounds of formula 18with at least about 0.2 molar equivalents, preferably from about 0.8 toabout 100 molar equivalents of a compound of formula 19 in the optionalpresence of a hydrogen halide acceptor in the optional presence of aninert organic solvent.

Typical hydrogen halide acceptors include alkali metal (preferablysodium or potassium) carbonates, bicarbonates, or lower alkyl carboxylicacid salts thereof (e.g., acetates).

Typical solvents include nitrohydrocarbons such as nitrobenzene and thelike; lower alkanols of 1-6 carbons such as ethanol, t-butanol, butanoland the like.

The reaction is carried out at from about 25° C. to about 300° C.,preferably from about 50° C. to about 250° C. for from about 0.2 hour toabout 96 hours, preferably from about 1 hour to about 48 hours.

The products of formula 15 are isolated by conventional techniques. Forexample the reaction is poured into excess dilute hydrochloric acid andextracted with ether. For products of formula 15 where m is zero, theether is dried, evaporated and the residual crude product ischromatographed.

For products of formula 15 where m is one, the above obtained aqueoushydrochloric acid extract is made alkaline to pH 9 and extracted withether. The ether is dried, evaporated and the residual product ischromatographed.

For compounds of formula 15 where m is zero see also Chemical Abstracts,43, 6175d (1948).

For compounds of formula 15 where m is one see also Proc. Indian Acad.Sci., 47A, 77 (1958).

For compounds of formula 16 see Acta Chem. Scand., 15,260 (1961).

The novel compounds of formula 1 are CNS depressants and are useful as,for example, sedatives, tranquilizers, hypnotics, anticonvulsants andmuscle relaxants in mammalian species, e.g. rats, mice and monkeys. Theyare also useful as feed additives for increasing growth rate and feedefficiency in mammalian species, such as livestock, specifically swineand cattle. The CNS depressant effects of compounds of this inventionare shown, for example, by the following tests in animals. Thus, forexample, oral administration of a compound of the invention producesataxia at dosage levels of from about 0.1 to about 10 mg/kg,specifically, in rats at about 3.1 mg/kg, in mice at about 1 mg/kg andin monkeys at about 2.5 mg/kg.

The compounds of the present invention produce a significanttranquilizing effect at a dosage level of from about 0.1 to about 25mg/kg, specifically at a dosage level of about 6.2 mg/kg whenadministered via the oral route to rats in a conflict test procedure[cf. J. R. Vogel, B. Beer, D. Clody, Psychopharmacologist, 21, 1(1970)].

In mice, oral administration of from about 0.1 to about 50 mg/kg of acompound of the present invention antagonizes the convulsant effects ofsubcutaneously administered pentylenetetrazole and of intraveneouslyadministered strychnine.

Mice treated with from about 0.01 to about 200 mg/kg of a compound ofthe present invention via the oral route increase significantly theirfood consumption.

The compounds of the present invention in the described dosages may beadministered orally; however, other routes such as intraperitoneally,subcutaneously, intramuscularly or intravenously may be employed.

The active compounds of the present invention are orally administered,for example, with an inert diluent or with an assimilable ediblecarrier, or they may be enclosed in hard or soft gelatin capsules, orthey may be compressed into tablets, or they may be incorporateddirectly with the food of the diet. For oral therapeutic administration,the active compounds of this invention may be incorporated withexcipients and used in the form of tablets, troches, capsules, elixirs,suspensions, syrups, wafers, chewing gum, and the like. Suchcompositions and preparations should contain at least 0.1% of activecompound. The percentage in the compositions and preparations may, ofcourse, be varied and may conveniently be between about 5% to about 75%or more of the weight of the unit. The amount of active compound in suchtherapeutically useful compositions or preparations is such that asuitable dosage will be obtained. Preferred compositions or preparationsaccording to the present invention are prepared so that an oral dosageunit form contains between about 10 and 500 milligrams of activecompound.

The tablets, troches, pills, capsules and the like may also contain thefollowing: a binder such as gum tragacanth, acacia, corn starch orgelatin; an excipient such as dicalcium phosphate; a disintegratingagent such as corn starch, potato starch, alginic acid and the like; alubricant such as magnesium stearate; and a sweetening agent such assucrose, lactose or saccharin may be added or a flavoring agent such aspeppermint, oil of wintergreen, or cherry flavoring. When the dosageunit form is a capsule, it may contain in addition to materials of theabove type a liquid carrier such as a fatty oil. Various other materialsmay be present as coatings or to otherwise modify the physical form ofthe dosage unit, for instance, tablets, pills or capsules may be coatedwith shellac, sugar or both. A syrup or elixir may contain the activecompounds, sucrose as a sweetening agent, methyl and propyl parabens aspreservatives, a dye and a flavoring such as cherry or orange flavor. Ofcourse, any material used in preparing any dosage unit form should bepharmaceutically pure and substantially non-toxic in the amountsemployed.

In the following examples all reactions are run under an inertatmosphere (e.g. argon), at room temperature, using anhydrous solventsunless otherwise indicated; in addition, reactions which are heated aresubsequently cooled to room temperature for work-up. In general,solvents are evaporated in a rotary flash vacuum apparatus. In thispatent application, the full name of the parent ring system of compoundsdescribed as indicated in Column I below is as indicated in Column II.

    ______________________________________                                        I                      II                                                     ______________________________________                                        "---4H-s-triazolo[4,3-a][1,5]-                                                                  "---5,6-dihydro-4H-s-                                       benzodiazepin---" triazolo[ 4,3-a][1,5]-                                                        benzodiazepin---"                                           "---1H-1,5-benzodiazepin---"                                                                    "---2,3,4,5-tetrahydro-1H-                                                    1,5-benzodiazepin---"                                       "---3H-1,5-benzodiazepin---"                                                                    "---4,5-dihydro-3H-1,5-                                                       benzodiazepin---"                                           ______________________________________                                    

EXAMPLE 1 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione

A solution of 28.6 g of7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione and 23.3 g ofphosphorous pentasulfide in 250 ml of pyridine is refluxed, withstirring, for 40 minutes under argon. The solvent is evaporated invacuo.

The residue is stirred in ice water and extracted with methylenechloride. The organic phase is washed consecutively with dilute aqueoushydrochloric acid, water and dried. The organic phase is filteredthrough a short column of neutral III alumina, the column is washed withethyl acetate and the filtrate evaporated. The residue is trituratedwith a small amount of hot benzene and the product filtered off anddried.

EXAMPLES 2-28

Following the procedure of Example 1 but substituting the compoundsindicated in Column I below for7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in Example 1, thecompounds indicated in Column II are obtained:

    ______________________________________                                                 I              II                                                    ______________________________________                                        2.    5-phenyl-1H-1,5-benzo-                                                                         5-phenyl-1H-1,5-benzo-                                       diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                3.    7-(trifluoromethyl)-5-                                                                         7-(trifluoromethyl)-5-                                       phenyl-1H-1,5-benzodia-                                                                        phenyl-1H-1,5-benzodia-                                      zepine-2,4-dione zepin-4-one-2-thione                                   4.    7-nitro-5-phenyl-1H-1,5-                                                                       7-nitro-5-phenyl-1H-                                         benzodiazepine-2,4-dione                                                                       1,5-benzodiazepin-4-                                                          one-2-thione                                           5.    7-methyl-5-phenyl-1H-                                                                          7-methyl-5-phenyl-1H-                                        1,5-benzodiazepine-                                                                            1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           6.    7-methoxy-5-phenyl-                                                                            7-methoxy-5-phenyl-1H-                                       1H-1,5-benzodia- 1,5-benzodiazepin-4-                                         zepine-2,4-dione one-2-thione                                           7.    7-(methylthio)-5-                                                                              7-(methylthio)-5-                                            phenyl-1H-1,5-benzo-                                                                           phenyl-1H-1,5-benzo-                                         diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                8.    7-pentyl-5-phenyl-1H-                                                                          7-pentyl-5-phenyl-1H- - 1,5-benzodiazepine- 1,5-ben                           zodiazepin-4-                                                2,4-dione        one-2-thione                                           9.    7-pentoxy-5-phenyl-                                                                            7-pentoxy-5-phenyl-1H-                                       1H-1,5-benzodiazepine-                                                                         1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           10.   7-bromo-5-phenyl-1H-                                                                           7-bromo-5-phenyl-1H-                                         1,5-benzodiazepine-                                                                            1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           11.   7-fluoro-5-phenyl-1H-                                                                          7-fluoro-5-phenyl-1H-                                        1,5-benzodiazepine-                                                                            1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           12.   7-cyano-5-phenyl-1H-                                                                           7-cyano-5-phenyl-1H-                                         1,5-benzodiazepine-                                                                            1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           13.   7-chloro-5-(2-chloro-                                                                          7-chloro-5-(2-chloro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzodia-                                     diazepine-2,4-dione                                                                            zepin-4-one-2-thione                                   14.   7-chloro-5-(2-fluoro-                                                                          7-chloro-5-(2-fluoro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                15.   7-chloro-5-(3-chloro-                                                                          7-chloro-5-(3-chloro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzodia-                                     diazepine-2,4-dione                                                                            zepin-4-one-2-thione                                   16.   7-chloro-5-(4-chloro-                                                                          7-chloro-5-(4-chloro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                17.   7-chloro-5-(2-methoxy-                                                                         7-chloro-5-(2-methoxy-                                       phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                18.   7-chloro-5-(3-methoxy-                                                                         7-chloro-5-(3-methoxy-                                       phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                19.   7-chloro-5-(4-methoxy-                                                                         7-chloro-5-(4-methoxy-                                       phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                20.   7-chloro-5-(2-methyl-                                                                          7-chloro-5-(2-methyl-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                21.   7-chloro-5-(3-methyl-                                                                          7-chloro-5-(3-methyl-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                22.   7-chloro-5-(4-methyl-                                                                          7-chloro-5-(4-methyl-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                23.   3-methyl-7-chloro-5-                                                                           3-methyl-7-chloro-5-                                         phenyl-1H-1,5-benzodia-                                                                        phenyl-1H-1,5-benzodia-                                      zepine-2,4-dione zepin-4-one-2-thione                                   24.   3-(benzyloxy)-7-chloro-                                                                        3-(benzyloxy)-7-chloro-                                      5-phenyl-1H-1,5-benzo-                                                                         5-phenyl-1H-1,5-benzo-                                       diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                25.   3-methoxy-7-chloro-5-                                                                          3-methoxy-7-chloro-5-                                        phenyl-1H-1,5-benzo-                                                                           phenyl-1H-1,5-benzo-                                         diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                26.   8-methyl-5-phenyl-1H-                                                                          8-methyl-5-phenyl-1H-                                        1,5-benzodiazepine-                                                                            1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           27.   8-chloro-5-phenyl-                                                                             8-chloro-5-phenyl-1H-                                        1H-1,5-benzodiazepine-                                                                         1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           28.   8-(trifluoromethyl)-5-                                                                         8-(trifluoromethyl)-5-                                       phenyl-1H-1,5-benzodia-                                                                        phenyl-1H-1,5-benzodia-                                      zepine-2,4-dione zepin-4-one-2-thione                                   ______________________________________                                    

EXAMPLE 291-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]-benzodiazepin-5-one

Method A

30.2 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione and 23.8g of acetic acid hydrazide in a mixture of 640 ml n-butanol and 160 mlof dimethyl sulfoxide are refluxed with stirring for 24 hours. Duringthis time, argon is bubbled through the reaction mixture. The reactionis concentrated in vacuo and partitioned between methylene chloride andwater; the organic phase is washed several times with water, dried andfiltered through a short Florisil column. After eluting the column withethyl acetate, the combined filtrates are evaporated to give the titlecompound. Recrystallization from ethanol-ethyl acetate, followed byvacuum drying at elevated temperatures gives the product.

Method B

15.8 g of 2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-oneand 8.1 g of acetic acid hydrazide in 400 ml dimethyl formamide arerefluxed with stirring for 24 hours. During this time nitrogen isbubbled through the reaction mixture. The reaction mixture is worked upas described in Example 29, Method A, to give the title compound.

Method C

A mixture of 6.2 g of1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one, 5 g ofcopper powder and 2.5 g of potassium acetate in 100 ml bromobenzene arerefluxed for six hours with stirring. The reaction is diluted withmethylene chloride, filtered through a short Florisil column and thefiltrate washed with dilute aqueous ammonium hydroxide. The organicphase is washed with water, dried and the solvent evaporated to give thetitle compound.

Method D

3.0 g of 2,7-dichloro-5-phenyl-3H-1,5-benzodiazepin-4-one and 1.8 g ofacetic acid hydrazide in 50 ml of dioxane are refluxed under argon for24 hours. 2 ml of water is then added, the reaction stirred for 1 hourand the solvent evaporated. The residue is taken up in methylenechloride, washed with dilute aqueous sodium bicarbonate, with water anddried. The solvent is evaporated and the residue is chromatographed onten-1000μ silica gel thick layer plates (20×20 cm) with ethylacetate-ethanol (9:1) as eluant. The main band, having an approximate Rfrange of 0.12-0.28, is removed, stirred with acetone-methanol (9:1) andthe silica gel filtered off. The filtrate is evaporated to give thetitle compound.

Method E

Following the procedure of Example 29, Method B, but substituting 15 gof 2-methoxy-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one for 15.8 g of2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in Example29, Method B, the title compound is obtained.

Method F

15 g of acetic acid2-(7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one-2-yl)hydrazide in 100 mldimethyl formamide are refluxed for 24 hours under a Soxhlet extractorcontaining 4A molecular sieves, under argon. The solvent is evaporatedand the crude product is purified as described in Example 29, Method D.

Method G

3.01 g of 2-hydrazino-7-chloro-5-phenyl-3H-1,5-benzdiazepin-4-one in 15ml of acetic anhydride is refluxed for 24 hours. The acetic anhydride isevaporated and the residual crude product taken up in methylene chlorideand purified as described in Example 29, Method D.

Method H

4.0 g of2-[2-(t-butoxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-onein 60 ml of n-butyl acetate which contains 2.0 g of hydrogen bromide isstirred at room temperature for 1 hour and refluxed for 24 hours. Thereaction is evaporated, the product dissolved in methylene chloride andpurified as described in Example 29, Method D.

Method I

To 4.96 g of1-methyl-8-chloro-4H-s-triazolo-[4,3-a][1,5]benzodiazepin-5-one in amixture of 70 ml ethanol and 200 ml of 0.1 N aqueous potassium hydroxideis added 7.2 g of diphenyliodonium bromide. The reaction is refluxed for8 hours. The iodobenzene is removed by steam distillation. Thedistillation residue is cooled and partitioned between methylenechloride and water. The organic phase is dried and evaporated to givethe title compound.

EXAMPLES 30-55

Following the procedure of Example 29, Method A, but substituting thecompounds indicated in Column I below for7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29,Method A, the compounds indicated in Column II are obtained.

    ______________________________________                                                 I              II                                                    ______________________________________                                        30.   5-phenyl-1H-1,5-benzo-                                                                         1-methyl-6-phenyl-4H-s-                                      diazepin-4-one-2-thione                                                                        triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    31.   7-(trifluoro-methyl)-5-                                                                        1-methyl-8-(trifluoro-                                       phenyl-1H-1,5-benzodia-                                                                        methyl)-6-phenyl-4H-s-                                       zepin-4-one-2-thione                                                                           triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    32.   7-nitro-5-phenyl-1H-                                                                           1-methyl-8-nitro-6-                                          1,5-benzodiazepin-4-                                                                           phenyl-4H-s-triazolo-                                        one-2-thione     [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            33.   7-methyl-5-phenyl-                                                                             1-methyl-8-methyl-6-                                         1H-1,5-benzodiazepin-                                                                          phenyl-4H-s-triazolo-                                        4-one-2-thione   [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            34.   7-methoxy-5-phenyl-                                                                            1-methyl-8-methoxy-                                          1H-1,5-benzodiazepin-                                                                          6-phenyl-4H-s-triazolo-                                      4-one-2-thione   [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            35.   7-(methylthio)-5-phenyl-                                                                       1-methyl-8-(methyl-                                          1H-1,5-benzodiazepin-                                                                          thio)-6-phenyl-4H-                                           4-one-2-thione   s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    36.   7-pentyl-5-phenyl-1H-                                                                          1-methyl-8-pentyl-6-                                         1,5-benzodiazepin-4-one-                                                                       phenyl-4H-s-triazolo-                                        2-thione         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            37.   7-pentoxy-5-phenyl-1H-                                                                         1-methyl-8-pentoxy-6-                                        1,5-benzodiazepin-4-                                                                           phenyl-4H-s-triazolo-                                        one-2-thione     [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            38.   7-bromo-5-phenyl-1H-                                                                           1-methyl-8-bromo-6-                                          1,5-benzodiazepin-4-                                                                           phenyl-4H-s-triazolo-                                        one-2-thione     [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            39.   7-fluoro-5-phenyl-1H-                                                                          1-methyl-8-fluoro-6-                                         1,5-benzodiazepin-4-                                                                           phenyl-4H-s-triazolo-                                        one-2-thione     [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            40.   7-cyano-5-phenyl-1H-                                                                           1-methyl-8-cyano-6-                                          1,5-benzodiazepin-4-                                                                           phenyl-4H-s-triazolo-                                        one-2-thione     [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            41.   7-chloro-5-(2-chloro-                                                                          1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (2-chlorophenyl)-4H-s-                                       diazepin-4-one-2-thione                                                                        triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    42.   7-chloro-5-(2-fluoro-                                                                          1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (2-fluorophenyl)-4H-                                         diazepin-4-one-2-thione                                                                        s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    43.   7-chloro-5-(3-chloro-                                                                          1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (3-chlorophenyl)-4H-                                         diazepin-4-one-2-thione                                                                        s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    44.   7-chloro-5-(4-chloro-                                                                          1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (4-chlorophenyl)-4H-s-                                       diazepin-4-one-2-thione                                                                        triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    45.   7-chloro-5-(2-methoxy-                                                                         1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (2-methoxyphenyl)-4H-                                        diazepin-4-one-2-thione                                                                        s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    46.   7-chloro-5-(3-methoxy-                                                                         1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (3-methoxyphenyl)-4H-                                        diazepin-4-one-2-thione                                                                        s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    47.   7-chloro-5-(2-methyl-                                                                          1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (2-methylphenyl)-4H-                                         diazepin-4-one-2-thione                                                                        s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    48.   7-chloro-5-(3-methyl-                                                                          1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (3-methylphenyl)-4H-                                         diazepin-4-one-2-thione                                                                        s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    49.   7-chloro-5-(4-methyl-                                                                          1-methyl-8-chloro-6-                                         phenyl)-1H-1,5-benzo-                                                                          (4-methylphenyl)-4H-                                         diazepin-4-one-2-thione                                                                        s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    50.   3-methyl-7-chloro-5-                                                                           1,4-dimethyl-8-chloro-                                       phenyl-1H-1,5-benzo-                                                                           6-phenyl-4H-s-triazolo-                                      diazepin-4-one-2-thione                                                                        [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            51.   3-(benzyloxy)-7-chloro-                                                                        4-(benzyloxy)-1-methyl-8-                                    5-phenyl-1H-1,5-benzodia-                                                                      chloro-6-phenyl-4H-s-                                        zepin-4-one-2-thione                                                                           triazolo-8 4,3-a][1,5]-                                                       benzodiazepin-5-one                                    52.   3-methoxy-7-chloro-5-                                                                          4-(methoxy)-1-methyl-8-                                      phenyl-1H-1,5-benzo-                                                                           chloro-6-phenyl-4H-s-                                        diazepin-4-one-2-thione                                                                        triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    53.   8-methyl-5-phenyl-1H-                                                                          1,9-dimethyl-6-phenyl-                                       1,5-benzodiazepin-4-                                                                           4H-s-triazolo[4,3-a]-                                        one-2-thione     [1,5]benzodiazepin-5-                                                         one                                                    54.   8-chloro-5-phenyl-1H-                                                                          9-chloro-1-methyl-6-                                         1,5-benzodiazepin-4-                                                                           phenyl-4H-s-triazolo-                                        one-2-thione     [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            55.   8-(trifluoromethyl)-5-                                                                         9-(trifluoromethyl)-                                         phenyl-1H-1,5-benzo-                                                                           1-methyl-6-phenyl-4H-                                        diazepin-4-one-2-                                                                              s-triazolo[4,3-a][1,5]-                                      thione           benzodiazepin-5-one                                    ______________________________________                                    

EXAMPLES 56-64

Following the procedure of Example 29, Method A, but substituting theacid hydrazides indicated in Column I below for acetic acid hydrazide inExample 29, Method A, the compounds indicated in Column II are obtained.

    ______________________________________                                                 I              II                                                    ______________________________________                                        56.   formic acid hydrazide                                                                          8-chloro-6-phenyl-4H-s-                                                       triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    57.   propionic acid hydrazide                                                                       1-ethyl-8-chloro-6-                                                           phenyl-4H-s-triazolo-                                                         [4,3-a][1,5]benzodiaze-                                                       pin-5-one                                              58.   valeric acid hydrazide                                                                         1-butyl-8-chloro-6-                                                           phenyl-4H-s-triazolo-                                                         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            59.   cyclopropane carboxylic                                                                        1-cyclopropyl-8-chloro-                                      acid hydrazide   6-phenyl-4H-s-triazolo-                                                       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            60.   cyclopentane carboxylic                                                                        1-cyclopentyl-8-chloro-                                      acid hydrazide   6-phenyl-4H-s-triazolo-                                                       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            61.   phenylacetic acid                                                                              1-benzyl-8-chloro-                                           hydrazide        6-phenyl-4H-s-triazolo-                                                       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            62.   2-methyl-propionic                                                                             1-isopropyl-8-chloro-                                        acid hydrazide   6-phenyl-4H-s-triazolo-                                                       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            63.   1-cyanoacetic acid                                                                             1-cyanomethyl-8-chloro-                                      hydrazide        6-phenyl-4H-s-triazolo-                                                       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            64.   benzoic acid hydrazide                                                                         1-phenyl-8-chloro-                                                            6-phenyl-4H-s-triazolo-                                                       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            ______________________________________                                    

EXAMPLES 65-91

Following the procedure of Example 29, Method A, but substituting formicacid hydrazide for acetic acid hydrazide in Example 29, Method A, andthe compounds indicated in Column I below for7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29,Method A, the compounds indicated in Column II are obtained.

    ______________________________________                                                 I              II                                                    ______________________________________                                        65.   5-phenyl-1H-1,5-benzodia-                                                                      6-phenyl-4H-                                                 zepin-4-one-2-thione                                                                           s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    66.   7-(trifluoromethyl)-5-                                                                         8-(trifluoro-                                                phenyl-1H-1,5-benzodia-                                                                        methyl)-6-phenyl-4H-s-                                       zepin-4-one-2-thione                                                                           triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    67.   7-nitro-5-phenyl-1H-                                                                           8-nitro-6-phenyl-4H-                                         1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    68.   7-methyl-5-phenyl-1H-                                                                          8-methyl-6-phenyl-4H-                                        1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    69.   7-methoxy-5-phenyl-1H-                                                                         8-methoxy-6-phenyl-4H-                                       1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    70.   7-(methylthio)-5-phenyl-                                                                       8-(methylthio)-6-phenyl-                                     1H-1,5-benzodiazepin-                                                                          4H-s-triazolo[4,3-a][1,5]-                                   4-one-2-thione   benzodiazepin-5-one                                    71.   7-pentyl-5-phenyl-1H-                                                                          8-pentyl-6-phenyl-4H-                                        1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    72.   7-pentoxy-5-phenyl-1H-                                                                         8-pentoxy-6-phenyl-4H-                                       1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    73.   7-bromo-5-phenyl-1H-                                                                           8-bromo-6-phenyl-4H-                                         1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    74.   7-fluoro-5-phenyl-1H-                                                                          8-fluoro-6-phenyl-4H-                                        1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    75.   7-cyano-5-phenyl-1H-                                                                           8-cyano-6-phenyl-4H-                                         1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    76.   7-chloro-5-(2-chloro-                                                                          8-chloro-6-(2-chloro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            77.   7-chloro-5-(2-fluoro-                                                                          8-chloro-6-(2-fluoro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            78.   7-chloro-5-(3-chloro-                                                                          8-chloro-6-(3-chloro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            79.   7-chloro-5-(4-chloro-                                                                          8-chloro-6-(4-chloro-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            80.   7-chloro-5-(2-methoxy-                                                                         8-chloro-6-(2-methoxy-                                       phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            81.   7-chloro-5-(3-methoxy-                                                                         8-chloro-6-(3-methoxy-                                       phenyl-1H-1,5-benzo-                                                                           phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            82.   7-chloro-5-(4-methoxy-                                                                         8-chloro-6-(4-methoxy-                                       phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            83.   7-chloro-5-(2-methyl-                                                                          8-chloro-6-(2-methyl-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            84.   7-chloro-5-(3-methyl-                                                                          8-chloro-6-(3-methyl-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl)-4H-s-triazolo-                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            85.   7-chloro-5-(4-methyl-                                                                          8-chloro-6-(4-methyl-                                        phenyl)-1H-1,5-benzo-                                                                          phenyl-4H-s-triazolo-                                        diazepin-4-one-2-thione                                                                        [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            86.   3-methyl-7-chloro-5-                                                                           4-methyl-8-chloro-6-                                         phenyl-1H-1,5-benzo-                                                                           phenyl-4H-s-triazolo-                                        diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            87.   3-(benzyloxy)-7-chloro-                                                                        4-(benzyloxy)-8-chloro-                                      5-phenyl-1H-1,5-benzo-                                                                         6-phenyl-4H-s-triazolo                                       diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            88.   3-methoxy-7-chloro-                                                                            4-methoxy-8-chloro-6-                                        5-phenyl-1H-1,5-benzo-                                                                         phenyl-4H-s-triazolo-                                        diazepin-4-one-2-                                                                              [4,3-a][1,5]  benzodia-                                      thione           zepin-5-one                                            89.   8-methyl-5-phenyl-1H-                                                                          9-methyl-6-phenyl-4H-                                        1,5-benzodiazepin-4-one-                                                                       s-triazolo[4,3-a][1,5]-                                      2-thione         benzodiazepin-5-one                                    90.   8-chloro-5-phenyl-1H-                                                                          9-chloro-6-phenyl-4H-                                        1,5-benzodiazepin-4-                                                                           s-triazolo[4,3-a][1,5]-                                      one-2-thione     benzodiazepin-5-one                                    91.   8-(trifluoromethyl)-                                                                           9-(trifluoromethyl)-6-                                       5-phenyl-1H-1,5-benzo-                                                                         phenyl-4H-s-triazolo-                                        diazepin-4-one-2-                                                                              [4,3-a][1,5]benzodia-                                        thione           zepin-5-one                                            ______________________________________                                    

EXAMPLE 92 2-(Methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one

To 3.03 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in asolution of 0.40 g sodium hydroxide and 15 ml of methanol is added, withstirring a solution of 1.39 g of methyl iodide in 5 ml of methanol.Stirring is continued for 1 hour, the reaction is evaporated, dilutedwith 30 ml methylene chloride and filtered through a short Florisilcolumn. After washing the column with ethyl acetate, the combinedfiltrates are evaporated to give the title compound.

EXAMPLES 93-96

Following the procedure of example 92 but substituting the compoundsindicated in column I below for methyl iodide and the compoundsindicated in column II for7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in example 92, thebenzodiazepinones indicated in column III are obtained.

    __________________________________________________________________________            I              II                III                                  __________________________________________________________________________    93. benzylbromide                                                                             7-(trifluoromethyl)-5-phenyl-                                                                   2-(benzylthio)-7-(trifluoromethyl)-                         1H-1,5-benzodiazepin-4-one-                                                                     5-phenyl-3H-1,5-benzodiazepin-                              2-thione          4-one                                       94. O-propyl p-toluene-                                                                       7-nitro-5-(o-chlorophenyl)-                                                                     2-(propylthio)-7-nitro-5-(o-                    sulfonate   1H-1,5-benzodiazepin-4-one-                                                                     chlorophenyl)-3H-1,5-benzodia-                              2-thione          zepin-4-one                                 95. methyl iodide                                                                             7-(trifluoromethyl)-5-phenyl-                                                                   2-(methylthio)-7-(trifluoromethyl)-                                           -  1H-1,5-benzodiazepin-4-one- 5-phenyl-                                      3H-1,5-benzodiazepin-                                       2-thione          4-one                                       96. dimethyl sulfate                                                                          7-chloro-5-benzyl-1H-1,5-                                                                       2-(methylthio)-7-chloro-                                    benzodiazepin-4-one-2-thione                                                                    5-benzyl-3H-1,5-benzodiazepin-                                                4-one                                       __________________________________________________________________________

EXAMPLES 97-102

Following the procedure of Example 92 but substituting the compoundsindicated in Column I below for7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 92, thecompounds indicated in Column II are obtained.

    ______________________________________                                                 I              II                                                    ______________________________________                                        97.   5-phenyl-1H-1,5- 2-(methylthio)-5-phenyl-                                     benzodiazepin-4-one-                                                                           3H-1,5-benzodiazepin-                                        2-thione         4-one                                                  98.   7-(trifluoromethyl)-5-                                                                         2-(methylthio)-7-(tri-                                       phenyl-1H-1,5-benzo-                                                                           fluoromethyl)-5-phenyl-                                      diazepin-4-one-2-                                                                              3H-1,5-benzodiazepin-                                        thione           4-one                                                  99.   7-nitro-5-phenyl-                                                                              2-(methylthio)-7-nitro-                                      1H-1,5-benzodiaze-                                                                             5-phenyl-3H-1,5-benzo-                                       pin-4-one-2-thione                                                                             diazepin-4-one                                         100.  7-methyl-5-phenyl-1H-                                                                          2-(methylthio)-7-methyl-                                     1,5-benzodiazepin-4-                                                                           5-phenyl-3H-1,5-benzo-                                       one-2-thione     diazepin-4-one                                         101.  7-methoxy-5-phenyl-                                                                            2-(methylthio)-7-methoxy-                                    1H-1,5-benzodiazepin-                                                                          5-phenyl-3H-1,5-benzo-                                       4-one-2-thione   diazepin-4-one                                         102.  7-(methylthio)-5-                                                                              2-(methylthio)-7-(methyl-                                    phenyl-1H-1,5-benzo-                                                                           thio)-5-phenyl-3H-1,5-                                       diazepin-4-one-2-                                                                              benzodiazepin-4-one                                          thione                                                                  ______________________________________                                    

EXAMPLES 103-109

Following the procedure of Example 29, Method B, but substituting thecompounds indicated in Column I below for acetic acid hydrazide inExample 29, Method B, the compounds indicated in Column II are obtained.

    ______________________________________                                                 I              II                                                    ______________________________________                                        103.  N,N-dimethylglycine-                                                                           1-[(Dimethylamino)-                                          hydrazide        methyl]-8-chloro-6-                                                           phenyl-4H-s-triazolo-                                                         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            104.  N,N-diethylglycine-                                                                            1-[(Diethylamino)-                                           hydrazide        methyl]-8-chloro-6-                                                           phenyl-4H-s-triazolo-                                                         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            105.  Pyrrolidinoacetic                                                                              1-[(1-Pyrrolidino)-                                          acid hydrazide   methyl]-8-chloro-6-                                                           phenyl-4H-s-triazolo-                                                         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            106.  4-Morpholinoacetic                                                                             1-(4-Morpholinomethyl)-                                      acid hydrazide   8-chloro-6-phenyl-4H-                                                         s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    107.  1-Piperidinoacetic acid                                                                        1-(1-Piperidinomethyl)-                                      hydrazide        8-chloro-6-phenyl-4H-                                                         s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    108.  N-Methylglycine  1-[(Methylamino)-methyl]-                                    hydrazide        8-chloro-6-phenyl-4H-                                                         s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    109.  2-(p-Methoxybenzyloxy)                                                                         1-[(p-Methoxybenzyloxy)-                                     acetic acid hydrazide                                                                          methyl]-8-chloro-6-                                                           phenyl-4H-2-triazolo-                                                         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            ______________________________________                                    

EXAMPLES 110-115

Following the procedure of Example 29, Method B, but substituting thecompounds indicated in Column I below for acetic acid hydrazide and thecompounds indicated in Column II below for2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in Example29, Method B, the compounds indicated in Column III are obtained.

    __________________________________________________________________________            I            II                  III                                  __________________________________________________________________________    110.                                                                              formic acid hydrazide                                                                     2-(methylthio)-7-chloro-5-                                                                      8-chloro-6-benzyl-4H-s-triazolo-                            benzyl-3H-1,5-benzodia-                                                                         [4,3-a][1,5]benzodiazepin-5-                                zepin-4-one       one                                         111.                                                                              acetic acid hydrazide                                                                     2-(methylthio)-7-chloro-5-                                                                      1-methyl-8-(-chloro-6-benzyl-4H-s-                          benzyl-3H-1,5-benzodia-                                                                         triazolo[4,3-a][1,5]benzodiazepin-                          zepin-4-one       5-one                                       112.                                                                              acetic acid hydrazide                                                                     2-(benzylthio)-7-(trifluoro-                                                                    1-methyl-8-(trifluoromethyl)-6-                             methyl)-5-phenyl-3H-1,5-                                                                        phenyl-4H-s-triazolo[4,3-a][1,5]-                           benzodiazepin-4-one                                                                             benzodiazepin-5-one                         113.                                                                              acetic acid hydrazide                                                                     2-(propylthio)-7-nitro-5-                                                                       1-methyl-8-nitro-6-(o-chloro-                               (o-chlorophenyl)-3H-1,5-                                                                        phenyl)-4H-s-triazolo[4,3-a]-                               benzodiazepin-4-one                                                                             [1,5]benzodiazepin-5-one                    114.                                                                              acetic acid hydrazide                                                                     2-(methylthio)-7-(trifluoro-                                                                    1-methyl-8-(trifluoromethyl)-6-                             methyl)-5-phenyl-3H-1,5-                                                                        phenyl-4H-s-triazolo[4,3-a]-                                benzodiazepin-4-one                                                                             [1,5]benzodiazepin-5-one                    115.                                                                              acetic acid hydrazide                                                                     2-(methylthio)-7-(trifluoromethyl)-                                                             1-methyl-8-(trifluoromethyl)-6-                             5-benzyl-3H-1,5-benzodiazepin-                                                                  benzyl-4H-s-triazolo[4,3-a][1,5]-                           4-one             benzodiazepin-5-one                         __________________________________________________________________________

EXAMPLES 116-121

Following the procedure of Example 29, Method B, but substituting thecompounds indicated in Column I below for2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in Example29, Method B, the compounds indicated in Column II are obtained.

    ______________________________________                                                 I              II                                                    ______________________________________                                        116.  2-(methylthio)-5-phenyl                                                                        1-methyl-6-phenyl-4H-s-                                      3H-1,5-benzodiazepin-4-                                                                        triazolo[4,3-a][1,5]-                                        one              benzodiazepin-5-one                                    117.  2-(methylthio)-7-(tri-                                                                         1-methyl-8-(trifluoromethyl)-                                fluoromethyl)-5-phenyl-                                                                        6-phenyl-4H-s-triazolo-                                      3H-1,5-benzodiazepin-                                                                          [4,3-a][1,5]benzodiazepin-                                   4-one            5-one                                                  118.  2-(methylthio)-7-nitro-                                                                        1-methyl-8-nitro-6-phenyl-                                   5-phenyl-3H-1,5-ben-                                                                           4H-s-triazolo[4,3-a][1,5]-                                   zodiazepin-4-one benzodiazepin-5-one                                    119.  2-(methylthio)-7-methyl-                                                                       1-methyl-8-methyl-6-phenyl-                                  5-phenyl-3H-1,5-ben-                                                                           4H-s-triazolo [4,3-a][1,5]-                                  zodiazepin-4-one benzodiazepin-5-one                                    120.  2-(methylthio)-7-methoxy-                                                                      1-methyl-8-methoxy-6-phen-                                   5-phenyl-3H-1,5-ben-                                                                           yl-4H-s-triazolo[4,3-a][1,5]-                                zodiazepin-4-one benzodiazepin-5-one                                    121.  2-(methylthio)-7-(methyl-                                                                      1-methyl-8-(methylthio)-6-                                   thio)-5-phenyl-3H-1,5-                                                                         phenyl-4H-s-triazolo[4,3-a]-                                 benzodiazepin-4-one                                                                            [1,5]benzodiazepin-5-                                                         one                                                    ______________________________________                                    

EXAMPLE 1221-(Hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

3.1 g of1-[(p-methoxybenzyloxy)-methyl]-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 30 ml acetic acid, at 25°, is stirred with 24 ml 48% aqueoushydrobromic acid for 20 minutes. The reaction is neutralized with 30%aqueous sodium hydroxide and extracted with chloroform. The organicphase is separated, washed with water, dried and the solvent evaporatedto give the title compound.

EXAMPLE 1231-(hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one,methanesulfonate

3.4 g of1-(hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 30 ml chloroform is reacted with 3.03 g triethylamine and then 3.44 gmethanesulfonyl chloride. The reaction is stirred at 20° for 90 minutes,washed with water, then with saturated aqueous sodium chloride anddried. The solvent is evaporated to give the title compound.

EXAMPLE 1241-(Diethylaminomethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

3.35 g of1-(Hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one,methanesulfonate in 15 ml dimethylsulfoxide at 0° is added dropwise withstirring to 3 ml of diethylamine in 10 ml dimethylsulfoxide. Thereaction is stirred at 20° for 2 hours, diluted with methylene chloride,washed with water and then saturated aqueous sodium chloride. Afterdrying, the solvent is evaporated to give the title compound.

EXAMPLES 125-132

Following the procedure of Example 124, but substituting the aminesindicated in Column I below for diethylamine amine in Example 124, thecompounds in Column II are obtained.

    ______________________________________                                        I                 11                                                          ______________________________________                                        125.   ammonia        1-(aminomethyl)-8-chloro-                                                     6-phenyl-4H-s-triazolo-                                                       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                             126.   methylamine    1-(methylaminomethyl)-                                                        8-chloro-6-phenyl-4H-                                                         s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                     127.   dimethylamine  1-(dimethylaminomethyl)-                                                      8-chloro-6-phenyl-4H-                                                         s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                     128.   pyrrolidine    1-[(1-pyrrolidino)-                                                           methyl]-8-chloro-6-                                                           phenyl-4H-s-triazolo-                                                         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                             129.   morpholine     1-(4-morpholinomethyl)-                                                       8-chloro-6-phenyl-4H-                                                         s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                     130.   2-ethanolamine 1-[[(2-hydroxyethyl)-                                                         amino]-methyl]-8-                                                             chloro-6-phenyl-4H-s-                                                         triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                     131.   piperidine     1-(piperidinomethyl)-                                                         8-chloro-6-phenyl-4H-                                                         s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                     132.   benzylamine    1-[(benzylamino)-methyl]-                                                     8-chloro-6-phenyl-4H-                                                         s-triazolo-[4,3-a][1,5]-                                                      benzodiazepin-5-one                                     ______________________________________                                    

EXAMPLE 133 2-Methoxy-7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one

To 11.4 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione stirredin 150 ml methanol is added, dropwise, approximately 2.1 g ofdiazomethane in ether. After addition is complete, the reaction isstirred for 1 hour and filtered. The filtrate is evaporated and theresidue diluted with a small amount of ether. The suspension is filteredand the filtrate evaporated to give the title compound.

EXAMPLE 1341-[[(Benzyloxycarbonyl)-amino]-methyl]-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

9.0 g of 2-methoxy-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one and 6.69g of 1-[(benzyloxycarbonyl)-amino]acetic acid hydrazide in 210 mln-butanol and 50 ml dimethyl sulfoxide are heated at 140° for 9 hours.The reaction is evaporated and the residue is worked up as described inExample 29, Method D, to give the title compound.

EXAMPLE 1351-(Aminomethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

4.5 g of1-[[(benzyloxycarbonyl)amino]-methyl]8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 60 ml acetic acid saturated with hydrogen bromide is stirred at 20°for 1 hour. The reaction mixture is concentrated to one-half itsoriginal volume in vacuo and diluted with ether. The precipitate isfiltered off, suspended in methylene chloride and shaken with excess 2 Naqueous sodium bicarbonate. The organic phase is separated, washed withwater, dried and evaporated to give the title compound.

EXAMPLE 1361-(Acetoxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

3.4 g of1-(hydroxymethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-oneand 1.0 g of acetic anhydride in 10 ml of pyridine are warmed in a steambath for 0.2 hour and stirred at room temperature for 10 hours. Thereaction mixture is cooled, diluted with 100 ml methylene chloride andwashed with 100 ml water containing 0.84 g sodium bicarbonate. Theorganic phase is washed four times with water, dried and evaporated. Theresidue is triturated with a minimum amount of ether and the titlecompound filtered off, dried and recrystallized from methylene chlorideand ether.

EXAMPLE 1374-Acetoxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

6.2 g of 8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one,3 g of N-chlorosuccinimide and 0.1 g of azodiisobutyronitrile in 200 mlbenzene are refluxed for 1 hour. The solvent is evaporated and theresidue (which contains4,8-dichloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one) isheated on a steam-bath for 10 minutes with 90 g of glacial acetic acidand 2.5 g of sodium acetate. The reaction is evaporated and the residuepartitioned between chloroform and dilute aqueous sodium bicarbonate.The chloroform is washed with water, dried and the solvent evaporated togive the title compound.

EXAMPLE 1384-Ethoxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

Following the procedure of Example 137 but substituting ethanol for boththe glacial acetic acid and the sodium acetate in Example 137, the titlecompound is obtained.

EXAMPLE 1394-Hydroxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

3.5 g of4-acetoxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-oneand 2.8 ml of 4 N aqueous sodium hydroxide in 160 ml of ethanol arestirred overnight at 25°. The reaction is neutralized with 0.5 g ofacetic acid and the solvent is evaporated. The residue is partitionedbetween chloroform and water, the organic phase is dried and the solventevaporated to give the title compound.

EXAMPLE 140 7-Chloro-5-benzyl-1H-1,5-benzodiazepine-2,4-dione

Method A

To a stirred refluxing solution of 22.3 g of2-benzylamino-4-chloroaniline in 400 ml benzene is added, dropwise, asolution of 13.8 g of malonyl dichloride in 45 ml benzene. Afteraddition is complete the reaction was refluxed for 7 hours, concentratedto 1/2 the original volume and cooled. The title compound is filteredoff and dried. The filtrate is evaporated and the residue recrystallizedfrom a mixture of ethanol-dimethylformamide to give additional product.

Method B

9.2 g of N-benzyl-N-(2'-amino-5'-chloro-phenyl)-malonamic acid, ethylester is added to a solution of 0.73 g of sodium in 100 ml ethanol.After refluxing for 2 hours the reaction is evaporated, the residuedissolved in water and acidified with hydroacetic acid. The titlecompound is filtered off and dried.

Method C

30 g of N-benzyl-N-(2'-nitro-5'-chloro-phenyl)-malonamic acid ethylester is added to a stirred suspension of 59 g iron powder, 360 ml ofethanol, 150 ml acetic acid and 105 ml water at reflux. After two hours,the reaction is filtered and the filtrate evaporated. The residue istreated with dilute aqueous ammonium hydroxide, extracted with methylenechloride, washed with water and dried. The solvent is evaporated and theresidue treated with ethanolic potassium hydroxide. The ethanol isevaporated, the residue taken up in water and acidified to pH 6 withhydrochloric acid. The title compound is filtered off and dried.

Method D

11 g of N-benzyl-N-(2'-amino-5'-chloro-phenyl)-malonamic acid ethylester in 50 ml ethanol containing 1.7 g potassium hydroxide is kept atroom temperature for 6 hours, refluxed to 45 minutes and the solventevaporated. The residue is taken up in water, neutralized to pH 7 withhydrochloric acid and the title compound filtered off and dried.

EXAMPLES 141-151

Following the procedure of Example 140, Method A, but substituting thecompounds indicated in Column I below for 2-benzylamino-4-chloroanilinein Example 140, Method A, the compounds in Column II are obtained.

    ______________________________________                                        I                  II                                                         ______________________________________                                        141.  2-benzylamino-4- 7-(trifluoromethyl-5-                                        (trifluoromethyl)aniline                                                                       benzyl-1H-1,5-benzodia-                                                       zepine-2,4-dione                                       142.  2-benzylamino-4- 7-methyl-5-benzyl-1H-                                        methylaniline    1,5-benzodiazepine-                                                           2,4-dione                                              143.  2-benzylamino-aniline                                                                          5-benzyl-1H-1,5-benzo-                                                        diazepine-2,4-dione                                    144.  2-benzylamino-4- 7-methoxy-5-benzyl-1H-                                       methoxyaniline   1,5-benzodiazepine-                                                           2,4-dione                                              145.  2-benzylamino-5- 8-chloro-5-benzyl-1H                                         chloroaniline    1,5-benzodiazepine-                                                           2,4-dione                                              146.  2-benzylamino-5- 8-(trifluoromethyl)-5-                                       (trifluoromethyl)aniline                                                                       benzyl-1H-1,5-benzo-                                                          diazepine-2,4-dione                                    147.  2-(p-methoxybenzyl-                                                                            7-chloro-5-(p-methoxy-                                       amino)-4-chloroaniline                                                                         benzyl)-1H-1,5-benzodia-                                                      zepine-2,4-dione                                       148.  2-(p-methoxybenzyl-                                                                            7-nitro-5-(p-methoxy-                                        amino)-4-nitroaniline                                                                          benzyl)-1H-1,5-benzo-                                                         diazepine-2,4-dione                                    149.  2-(p-methoxybenzyl-                                                                            7-methyoxy-5-(p-methoxy-                                     amino)-4-methoxy-                                                                              benzyl)-1H-1,5-benzo-                                        aniline          diazepine-2,4-dione                                    150.  2-(p-methoxybenzyl-                                                                            7-methyl-5-(p-methoxy-                                       (amino)-4-methyl-                                                                              benzyl)-1H-1,5-benzo-                                        aniline          diazepine-2,4-dione                                    151.  2-(o,p-dimethoxy-                                                                              7-(trifluoromethyl)-5-                                       benzylamino)-4-  (o,p-dimethoxybenzyl)-                                       (trifluoromethyl)                                                                              1H-1,5-benzodiazepine-                                       methylaniline    2,4-dione-                                             ______________________________________                                    

EXAMPLES 152-164

Following the procedure of Example 1 but substituting the compoundsindicated in Column 1 below for7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in Example 1, thecompounds indicated in Column II are obtained.

    ______________________________________                                        I                  II                                                         ______________________________________                                        152.  5-benzyl-1H-1,5-benzo-                                                                         5-benzyl-1H-1,5-benzo-                                       diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                153.  7-chloro-5-benzyl-1H-                                                                          7-chloro-5-benzyl-                                           1,5-benzodiazepine-                                                                            1H-1,5-benzodiazepin-                                        2,4-dione        4-one-2-thione                                         154.  7-methyl-5-benzyl-1H-                                                                          7-methyl-5-benzyl-1H-                                        1,5-benzodiazepine-                                                                            1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           155.  7-methoxy-5-benzyl-1H-                                                                         7-methoxy-5-benzyl-1H-                                       1,5-benzodiazepine                                                                             1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           156.  8-(trifluoromethyl)-5-                                                                         8-(trifluoromethyl)-5-                                       benzyl-1H-1,5-benzodia-                                                                        benzyl-1H-1,5-benzo-                                         zepine-2,4-dione diazepin-4-one-2-thione                                157.  8-chloro-5-benzyl-1H-                                                                          8-chloro-5-benzyl-1H-                                        1,5-benzodiazepine-                                                                            1,5-benzodiazepin-4-                                         2,4-dione        one-2-thione                                           158.  7-(trifluoromethyl)-5-                                                                         7-(trifluoromethyl)-5-                                       benzyl-1H-1,5-benzo-                                                                           benzyl-1H-1,5-benzo-                                         diazepine-2,4-dione                                                                            diazepin-4-one-2-thione                                159.  7-chloro-5-(p-methoxy-                                                                         7-chloro-5-(p-methoxy-                                       benzyl)-1H-1,5-benzo-                                                                          benzyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-                                                             thione                                                 160.  7-nitro-5-(p-methoxy-                                                                          7-nitro-5-(p-methoxy-                                        benzyl)-1H-1,5-benzo-                                                                          benzyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-                                                             thione                                                 161.  7-methoxy-5-(p-methoxy-                                                                        7-methoxy-5-(p-methoxy-                                      benzyl)-1H-1,5-benzo-                                                                          benzyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-                                                             thione                                                 162.  7-methyl-5-(p-methoxy-                                                                         7-methyl-5-(p-methoxy-                                       benzyl)-1H-1,5-benzo-                                                                          benzyl)-1H-1,5-benzo-                                        diazepine-2,4-dione                                                                            diazepin-4-one-2-                                                             thione                                                 163.  7-trifluoromethyl)-5-                                                                          7-(trifluoromethyl)-5-                                       (p-methoxybenzyl)-1H-                                                                          (p-methoxybenzyl)-                                           1,5-benzodiazepine-2,4-                                                                        1H-1,5-benzodiazepin-                                        dione            4-one-2-thione                                         164.  7-(trifluoromethyl)-5-                                                                         7-(trifluoromethyl)-5-                                       (o,p-dimethyoxybenzyl)-                                                                        (o,p-dimethoxybenzyl)-                                       1H-1,5-benzodiazepine-                                                                         1H-1,5-benzodiazepin-                                        2,4-dione        4-one-2-thione                                         ______________________________________                                    

EXAMPLES 165-177

Following the procedure of Example 29, Method A, but substituting thecompounds indicated in Column I below for7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29,Method A, the compounds indicated in Column II are obtained.

    ______________________________________                                        I                  II                                                         ______________________________________                                        165.  5-benzyl-1H-1,5-benzo-                                                                         1-methyl-6-benzyl-4H-                                        diazepin-4-one-2-thione                                                                        s-triazolo[4,3-8][1,5]-                                                       benzodiazepin-5-one                                    166.  7-chloro-5-benzyl-1H-                                                                          1-methyl-8-chloro-6-                                         1,5-benzodiazepin-4-one-                                                                       benzyl-4H-s-triazolo-                                        2-thione         [4,3-1][1,5]benzodia-                                                         zepin-5-one                                            167.  7-methyl-5-benzyl-1H-                                                                          1-methyl-8-methyl-6-                                         1,5-benzodiazepin-4-                                                                           benzyl-4H-s-triazolo-                                        one-2-thione     [4,3-1][1,5]benzodia-                                                         zepin-5-one                                            168.  7-methoxy-5-benzyl-1H-                                                                         1-methyl-8-methoxy-6-                                        1,5-benzodiazepin-4-                                                                           benzyl-4H-s-triazolo-                                        one-2-thione     [4,3-1][1,5]benzodia-                                                         zepin-5-one                                            169.  8-(trifluoromthyl)-5-                                                                          1-methyl-9-(trifluoro-                                       benzyl-1H-1,5-benzodia-                                                                        methyl)-6-benzyl-4H-s-                                       zepin-4-one-2-thione                                                                           triazolo[4,3-1][1,5]-                                                         benzodiazepin-5-one                                    170.  8-chloro-5-benzyl-1H-                                                                          1-methyl-9-chloro-6-                                         1,5-benzodiazepin-4-                                                                           benzyl-4H-s-triazolo-                                        one-2-thione     [4,3-a][1,5]benzo-                                                            diazepin-5-one                                         171.  7-(trifluoromethyl)-5-                                                                         1-methyl-8-(trifluoro-                                       benzyl-1H-1,5-benzodia-                                                                        methyl)-6-benzyl-4H-s-                                       zepin-4-one-2-thione                                                                           triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    172.  7-chloro-5-(p-methoxy-                                                                         1-methyl-8-chloro-6-                                         benzyl)-1H-1,5-benzo-                                                                          (p-methoxybenzyl)-4H-                                        diazepin-4-one-2-                                                                              s-triazolo[4,3-a][1,5]-                                      thione           benzodiazepin-5-one                                    173.  7-nitro-5-(p-methoxy-                                                                          1-methyl-8-nitro-6-                                          benzyl)-1H-1,5-benzo-                                                                          (p-methoxybenzyl)-4H-                                        diazepin-4-one-2-                                                                              s-triazolo[4,3-a][1,5]-                                      thione           benzodiazepin-5-one                                    174.  7-methoxy-5-(p-methoxy-                                                                        1-methyl-8-methoxy-6-                                        benzyl)-1H-1,5-benzo-                                                                          (p-methoxybenzyl)-4H-                                        diazepin-4-one-2-                                                                              s-triazolo[4,3-a][1,5]-                                      thione           benzodiazepin-5-one                                    175.  7-methyl-5-(p-methoxy-                                                                         1-methyl-8-methyl-6-                                         benzyl)-1H-1,5-benzo-                                                                          (p-methoxybenzyl)-4H-                                        diazepin-4-one-2-                                                                              s-triazolo[4,3-a][1,5]-                                      thione           benzodiazepin-5-one                                    176.  7-(trifluoromethyl)-5-                                                                         1-methyl-8-(trifluoro-                                       (p-methoxybenzyl)-1H-                                                                          methyl)-6-(p-methoxy-                                        1,5-benzodiazepin-4-one-                                                                       benzyl)-4H-s-triazolo                                        2-thione         [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            177.  7-(trifluoromethyl)-5-                                                                         1-methyl-8-(trifluoro-                                       (o,p-dimethoxybenzyl)-                                                                         methyl)-6-(o,p-dimethoxy-                                    1H-1,5-benzodiazepin-                                                                          benzyl)-4H-s-triazolo-                                       4-one-2-thione   [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            ______________________________________                                    

EXAMPLES 178-189

Following the procedure of Example 29, Method A, but substituting theacid hydrazides indicated in Column I below for acetic acid hydrazideand the compounds indicated in column II below for7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in Example 29,Method A, the compounds in Column III are obtained:

    __________________________________________________________________________    I              II              III                                            __________________________________________________________________________    178.                                                                             formic acid hydrazide                                                                     7-chloro-5-benzyl-1H-1,5-benzo-                                                               8-chloro-6-benzyl-4H-s-triazolo-                              diazepin-4-one-2-thione                                                                       [4,3-a][1,5]benzodiazepin-5-one                179.                                                                             propionic acid hydra-                                                                     7-chloro-5-benzyl-1H-1,5-benzo-                                                               1-ethyl-8-chloro-6-benzyl-4H-s-                   zide        diazepin-4-one-2-thione                                                                       triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                    180.                                                                             cyclopropane carboxylic                                                                   7-chloro-5-benzyl-1H-1,5-benzo-                                                               1-cyclopropyl-8-chloro-6-                         acid hydrazide                                                                            diazepin-4-one-2-thione                                                                       benzyl-4H-s-triazolo[4,3-a]-                                                  [1,5]benzodiazepin-5-one                       181.                                                                             N,N-dimethyl-                                                                             7-chloro-5-benzyl-1H-1,5-benzo-                                                               1-[dimethylamino)methyl]-8-                       aminoglycine hydrazide                                                                    diazepin-4-one-2-thione                                                                       chloro-6-benzyl-4H-s-triazolo-                                                [4,3-a][1,5]benzodiazepin-5-                                                  one                                            182.                                                                             formic acid 7-(trifluoromethyl)-5-(p-                                                                     8-(trifluoromethyl)-6-(p-methoxy-                 hydrazide   methoxybenzyl)-1H-1,5-benzo-                                                                  benzyl)-4H-s-triazolo[4,3-a]-                                 diazepin-4-one-2-thione                                                                       [1,5]benzodiazepin-5-one                       183.                                                                             propionic acid                                                                            7-(trifluoromethyl)-5-(p-                                                                     1-ethyl-8-(trifluoromethyl)-6-                    hydrazide   methoxybenzyl)-1H-1,5-benzo-                                                                  (p-methoxybenzyl)-4H-s-triazolo-                              diazepin-4-one-2-thione                                                                       [4,3-a][1,5]benzodiazepin-5-one                184.                                                                             cyclopropane                                                                              7-(trifluoromethyl)-5-(p-                                                                     1-cyclopropyl-8-(trifluoromethyl)-                carboxylic acid                                                                           methoxybenzyl)-1H-1,5-benzo-                                                                  6-(p-methoxybenzyl)-4H-s-                         hydrazide   diazepin-4-one-2-thione                                                                       triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                    185.                                                                             N,N-dimethyl-                                                                             7-(trifluoromethyl)-5-(p-                                                                     1-[(dimethylamino)methyl]-8-                      aminoglycine                                                                              methoxybenzyl)-1H-1,5-benzo-                                                                  (trifluoromethyl)-6-(p-methoxy-                   hydrazide   diazepin-4-one-2-thione                                                                       benzyl)-4H-s-triazolo[4,3-a]-                                                 [1,5]benzodiazepin-5-one                       186.                                                                             formic acid 7-nitro-5-(p-methoxybenzyl)-                                                                  8-nitro-6-(p-methoxybenzyl)-                      hydrazide   1H-1,5-benzodiazepin-4-one-                                                                   4H-s-triazolo[4,3-a]  [1,5]-                                  2-thione        benzodiazepin-5-one                            187.                                                                             propionic acid                                                                            7-nitro-5-(p-methoxybenzyl)-                                                                  1-ethyl-8-nitro-6-(p-methoxy-                     hydrazide   1H-1,5-benzodiazepin-4-one-                                                                   benzyl)-4H-s-triazolo[4,3-a]-                                 2-thione        [1,5]benzodiazepin-5-one                       188.                                                                             cyclopropane                                                                              7-nitro-5-(p-methoxybenzyl)-                                                                  1-cyclopropyl-8-nitro-6-                          carboxylic acid                                                                           1H-1,5-benzodiazepin-4-one-                                                                   (p-methoxybenzyl)-4H-s-tria-                      hydrazide   2-thione        zolo[4,3-a][1,5]benzodiazepin-                                                5-one                                          189.                                                                             N,N-dimethyl-                                                                             7-nitro-5-(p-methoxybenzyl)-                                                                  1-[(dimethylamino)methyl]-8-                      aminoglycine                                                                              1H-1,5-benzodiazepin-4-one-                                                                   nitro-6-(p-methoxybenzyl)-                        hydrazide   2-thione        4H-s-triazolo[4,3-a][1,5]-                                                    benzodiazepin-5-one                            __________________________________________________________________________

EXAMPLE 190 8-Chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

Method A

2.92 g of 8-chloro-6-benzyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 300 ml acetic acid containing 0.3 g of pre-reduced Raney nickelcatalyst is hydrogenated at 60° starting with an initial hydrogenpressure of 60 p.s.i. The reduction is stopped after 0.01 mole ofhydrogen has been absorbed, the catalyst filtered off and the solventevaporated. The residue is stirred with water and the title compound isfiltered off and dried.

Method B

2.92 g of8-chloro-6-(p-methoxybenzyl)-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 100 ml of anhydrous hydrogen fluoride is stirred at 20° C. for onehour. The hydrogen fluoride is then evaporated; the residue ispartitioned between methylene chloride and dilute aqueous sodiumbicarbonate. The organic phase is washed with water, dried andevaporated. The residue is stirred with ether and the title compound isfiltered off and dried.

EXAMPLES 191-201

Following the procedure of Example 190, Method A, but substituting thecompounds indicated in Column I below for8-chloro-6-benzyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one inExample 190, Method A, the compounds indicated in Column II areobtained.

    ______________________________________                                        I                  II                                                         ______________________________________                                        191.  1-methyl-6-benzyl-4H-s-                                                                        1-methyl-4H-s-triazolo-                                      triazolo[4,3-a][1,5]ben-                                                                       [4,3-a][1,5]benzodia-                                        zodiazepin-5-one zepin-5-one                                            192.  1-methyl-8-chloro-6-                                                                           1-methyl-8-chloro-4H-                                        benzyl-4H-s-triazolo-                                                                          s-triazolo[4,3-a][1,5]-                                      [4,3-a][1,5]benzodia-                                                                          benzodiazepin-5-one                                          zepin-5-one                                                             193.  1-methyl-8-methyl-6-                                                                           1-methyl-8-methyl-4H-                                        benzyl-4H-s-triazolo-                                                                          s-triazolo[4,3-a][1,5]-                                      [4,3-a][1,5]benzodia-                                                                          benzodiazepin-5-one                                          zepin-5-one                                                             194.  1-methyl-8-methoxy-                                                                            1-methyl-8-methoxy-                                          6-benzyl-4H-s-triazolo-                                                                        4H-s-triazolo[4,3-a]-                                        [4,3-a][1,5]benzodia-                                                                          [1,5]benzodiazepin-5-                                        zepin-5-one      one                                                    195.  1-methyl-9-(trifluoro-                                                                         1-methyl-9-(trifluoro-                                       methyl)-6-benzyl-4H-                                                                           methyl)-4H-s-triazolo-                                       s-triazolo[4,3-a]-                                                                             [4,3-a][1,5]benzodia-                                        [1,5]benzodiazepin-                                                                            zepin-5-one                                                  5-one                                                                   196.  1-methyl-9-chloro-6-                                                                           1-methyl-9-chloro-                                           benzyl-4H-s-triazolo-                                                                          4H-s-triazolo[4,3-a]-                                        [4,3-a][1,5]benzodia-                                                                          [1,5]benzodiazepin-                                          zepin-5-one      5-one                                                  197.  1-methyl-8-(trifluoro-                                                                         1-methyl-8-(trifluoro-                                       methyl)-6-benzyl-4H-                                                                           methyl)-4H-s-triazolo-                                       s-triazolo[4,3-a]-                                                                             [4,3-a][1,5]benzodia-                                        [1,5]benzodiazepin-                                                                            zepin-5-one                                                  5-one                                                                   198.  8-chloro-6-benzyl-4H-                                                                          8-chloro-4H-s-triazolo-                                      s-triazolo[4,3-a][1,5]-                                                                        [4,3-a][1,5]benzodia-                                        benzodiazepin-5-one                                                                            zepin-5-one                                            199.  1-ethyl-8-chloro-6-                                                                            1-ethyl-8-chloro-4H-                                         benzyl-4H-s-triazolo-                                                                          s-triazolo[4,3-a][1,5]-                                      [4,3-a][1,5]benzo-                                                                             benzodiazepin-5-one                                          diazepin-5-one                                                          200.  1-cyclopropyl-8-chloro-                                                                        1-cyclopropyl-8-chloro-                                      6-benzyl-4H-s-triazolo-                                                                        4H-s-triazolo[4,3-a]-                                        [4,3-a][1,5]benzodia-                                                                          [ 1,5]benzodiazepin-5-                                       zepin-5-one      one                                                    201.  1-[(dimethylamino)-                                                                            1-[(dimethylamino)-                                          methyl]-8-chloro-6-                                                                            methyl]-8-chloro-4H-                                         benzyl-4H-s-triazolo-                                                                          s-triazolo[4,3-a][1,5]-                                      [4,3-a][1,5]benzodia-                                                                          benzodiazepin-5-one                                          zepin-5-one                                                             ______________________________________                                    

EXAMPLES 202-215

Following the procedure of Example 190, Method B, but substituting thecompounds indicated in Column I below for8-chloro-6-(p-methoxybenzyl)-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein Examples 190, Method B, the compounds indicated in Column II areobtained.

    ______________________________________                                        I                 II                                                          ______________________________________                                        202. 8-(trifluoromethyl)-6-                                                                         8-(trifluoromethyl)-4H-                                      (p-methoxybenzyl)-4H-                                                                          s-triazolo[4,3-a][1,5]-                                      s-triazolo[4,3-a][1,5]-                                                                        benzodiazepin-5-one                                          benzodiazepin-5-one                                                      203. 1-ethyl-8-(trifluoro-                                                                          1-ethyl-8-(trifluoro-                                        methyl)-6-(p-methoxy-                                                                          methyl)-4H-s-triazolo-                                       benzyl)-4H-s-triazolo-                                                                         [4,3-a][1,5]benzodia-                                        [4,3-a][1,5]benzodia-                                                                          zepin-5-one                                                  zepin-5-one                                                              204. 1-cyclopropyl-8-(tri-                                                                          1-cyclopropyl-8-(tri-                                        fluoromethyl)-6-(p-                                                                            fluoromethyl)-4H-s-                                          methoxybenzyl)-4H-s-                                                                           triazolo[4,3-a][1,5]-                                        triazolo[4,3-a][1,5]-                                                                          benzodiazepin-5-one                                          benzodiazepin-5-one                                                      205. 1-[(dimethylamino)-                                                                            1-[(dimethylamino)-                                          methyl]-8-(trifluoro-                                                                          methyl]-8-(trifluoro-                                        methyl)-6-(p-methoxy-                                                                          methyl)-4H-s-triazolo-                                       benzyl-4H-s-triazolo-                                                                          [4,3-a][1,5]benzodia-                                        [4,3-a][1,5]benzodia-                                                                          zepin-5-one                                                  zepin-5-one                                                              206. 8-nitro-6-(p-methoxy-                                                                          8-nitro-4H-s-triazolo-                                       benzyl)-4H-s-triazolo-                                                                         [4,3-a][1,5]benzodia-                                        [4,3-a][1,5]benzodia-                                                                          zepin-5-one                                                  zepin-5-one                                                              207. 1-ethyl-8-nitro-6-(p-                                                                          1-ethyl-8-nitro-4H-s-                                        methoxybenzyl)-4H-s-                                                                           triazolo[4,3-a][1,5]-                                        triazolo[4,3-a][1,5]-                                                                          benzodiazepin-5-one                                          benzediazepin-5-one                                                      208. 1-cyclopropyl-8-nitro-                                                                         1-cyclopropyl-8-nitro-                                       6-(p-methoxybenzyl)-                                                                           4H-s-triazolo[4,3-a]-                                        4H-s-triazolo[4,3-a]-                                                                          [1,5]benzodiazepin-                                          [1,5]benzodiazepin-                                                                            5-one                                                        5-one                                                                    209. 1-[dimethylamino)-                                                                             1-[(dimethylamino)-                                          methyl]-8-nitro-6-(p-                                                                          methyl]-8-nitro-4H-s-                                        methoxybenzyl)-4H-s-                                                                           triazolo[4,3-a][1,5]-                                        triazolo[4,3-a][1,5]-                                                                          benzodiazepin-5-one                                          benzodiazepin-5-one                                                      210. 1-methyl-8-chloro-6-                                                                           1-methyl-8-chloro-4H-                                        (p-methoxybenzyl)-4H-                                                                          s-triazolo[4,3-a][1,5]-                                      s-triazolo[ 4,3-a][1,5]-                                                                       benzodiazepin-5-one                                          benzodiazepin-5-one                                                      211. 1-methyl-8-nitro-6-                                                                            1-methyl-8-nitro-4H-                                         (p-methoxybenzyl)-4H-                                                                          s-triazolo[4,3-a][1,5]-                                      s-triazolo[4,3-a][1,5]-                                                                        benzodiazepin-5-one                                          benzodiazepin-5-one                                                      212. 1-methyl-8-methoxy-6-                                                                          1-methyl-8-methoxy-                                          (p-methoxybenzyl)-4H-                                                                          4H-s-triazolo[4,3-a]-                                        s-triazolo[4,3-a][1,5]-                                                                        [1,5]benzodiazepin-5-                                        benzodiazepin-5-one                                                                            one                                                     213. 1-methyl-8-methyl-6-                                                                           1-methyl-8-methyl-                                           (p-methoxybenzyl)-4H-                                                                          4H-s-triazolo[4,3-a]-                                        s-triazolo[4,3-a][1,5]-                                                                        [1,5]benzodiazepin-5-                                        benzodiazepin-5-one                                                                            one                                                     214. 1-methyl-8-(trifluoro-                                                                         1-methyl-8-(trifluoro-                                       methyl)-6-(p-methoxy-                                                                          methyl)-4H-s-triazolo-                                       benzyl)-4H-s-triazolo-                                                                         [4,3-a][1,5]benzodia-                                        [4,3-a][1,5]benzodia-                                                                          zepin-5-one                                                  zepin-5-one                                                              215. 1-methyl-8-(trifluoro-                                                                         1-methyl-8-(trifluoro-                                       methyl)-6-(o,p-dimethoxy-                                                                      methyl)-4H-s-triazolo-                                       benzyl)-4H-s-triazolo-                                                                         [4,3-a][1,5]benzodia-                                        [4,3-a][1,5]benzodia                                                                           zepin-5-one                                                  zepin-5-one                                                              ______________________________________                                    

EXAMPLES 216-235

Following the procedure of Example 29, Methods C or I, but substitutingthe compounds indicated in Column I below for1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one inExample 29, Methods C or I, the compounds indicated in Column II areobtained.

    ______________________________________                                        I                  II                                                         ______________________________________                                        216. 1-methyl-4H-s-triazolo-                                                                         1-methyl-6-phenyl-4H-                                       [4,3-a][1,5]benzodia-                                                                           s-triazolo[4,3-a][1,5]-                                     zepin-5-one       benzodiazepin-5-one                                    217. 1-methyl-8-chloro-4H-                                                                           1-methyl-8-chloro-6-                                        s-triazolo[4,3-a][1,5]-                                                                         phenyl-4H-s-triazolo-                                       benzodiazepin-5-one                                                                             [4,3-a][1,5]benzodiaze-                                                       pin-5-one                                              218. 1-methyl-8-methoxy-4H-                                                                          1-methyl-8-methoxy-6-                                       s-triazolo[4,3-a][1,5]-                                                                         phenyl-4H-s-triazolo-                                       benzodiazepin-5-one                                                                             [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            219. 1-methyl-8-(trifluoro-                                                                          1-methyl-8-(trifluoro-                                      methyl)-4H-s-triazolo-                                                                          methyl)-6-phenyl-4H-                                        [4,3-a][1,5]benzodia-                                                                           s-triazolo[4,3-a][1,5]-                                     zepin-5-one       benzodiazepin-5-one                                    220. 1-methyl-8-nitro-4H-                                                                            1-methyl-8-nitro-6-                                         s-triazolo[4,3-a][1,5]-                                                                         phenyl-4H-s-triazolo-                                       benzodiazepin-5-one                                                                             [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            221. 1-methyl-9-chloro-                                                                              1-methyl-9-chloro-6-                                        4H-s-triazolo[4,3-a]-                                                                           phenyl-4H-s-triazolo-                                       [1,5]benzodiazepin-5-                                                                           [4,3-a][1,5]benzodia-                                       one               zepin-5-one                                            222. 1-methyl-9-(trifluoro-                                                                          1-methyl-9-(trifluoro-                                      methyl)-4H-s-triazolo-                                                                          methyl)-6-phenyl-4H-                                        [4,3-a][1,5]benzodia-                                                                           s-triazolo[4,3-a]-                                          zepin-5-one       [1,5]benzodiazepin-                                                           5-one                                                  223. 1,8-dimethyl-4H-s-                                                                              1,8-dimethyl-6-phenyl-                                      triazolo[4,3-a][1,5]-                                                                           4H-s-triazolo[4,3-a]-                                       benzodiazepin-5-one                                                                             [1,5]benzodiazepin-                                                           5-one                                                  224. 8-(trifluoromethyl)-4H-                                                                         8-(trifluoromethyl)-6-                                      s-triazolo[4,3-a][1,5]-                                                                         phenyl-4H-s-triazolo-                                       benzodiazepin-5-one                                                                             [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            225. 1-ethyl-8-(trifluoro-                                                                           1-ethyl-8-(trifluoro-                                       methyl)-4H-s-triazolo-                                                                          methyl)-6-phenyl-4H-                                        [4,3-a][ 1,5]benzodia-                                                                          s-triazolo [4,3-a][1,5]-                                    zepin-5-one       benzodiazepin-5-one                                    226. 1-cyclopropyl-8-(tri-                                                                           1-cyclopropyl-8-(tri-                                       fluoromethyl)-4H-s-                                                                             fluoromethyl)-6-phenyl-                                     triazolo[4,3-a][1,5]-                                                                           4H-s-triazolo[4,3-a]-                                       benzodiazepin-5-one                                                                             [1,5]benzodiazepin-                                                           5-one                                                  227. 1-[(dimethylamino)-                                                                             1-[(dimethylamino)-                                         methyl]-8-(trifluoro-                                                                           methyl]-8-(trifluoro-                                       methyl)-4H-s-triazolo-                                                                          methyl)-6-phenyl-4H-                                        [4,3-a][1,5]benzo-                                                                              s-triazolo[4,3-a][1,5]-                                     diazepin-5-one    benzodiazepin-5-one                                    228. 8-nitro-4H-s-triazolo-                                                                          8-nitro-6-phenyl-4H-                                        [4,3-a][1,5]benzodia-                                                                           s-triazolo[4,3-a]-                                          zepin-5-one       [1,5]benzodiazepin-                                                           5-one                                                  229. 1-ethyl-8-nitro-4H-                                                                             1-ethyl-8-nitro-6-                                          s-triazolo[4,3-a]-                                                                              phenyl-4H-s-triazolo-                                       [1,5]benzodiazepin-                                                                             [4,3-a][1,5]benzodia-                                       5-one             zepin-5-one                                            230. 1-cyclopropyl-8-nitro-                                                                          1-cyclopropyl-8-nitro-                                      4H-s-triazolo[4,3-a]-                                                                           6-phenyl-4H-s-triazolo-                                     [1,5]benzodiazepin-5-                                                                           [4,3-a][1,5]benzodia-                                       one               zepin-5-one                                            231. 1-[(dimethylamino)-                                                                             1-[(dimethylamino)-                                         methyl]-8-nitro-4H-                                                                             methyl]-8-nitro-6-                                          s-triazolo[4,3-a]-                                                                              phenyl-4H-s-triazolo-                                       [1,5]benzodiazepin-                                                                             [4,3-a][1,5]benzodia-                                       5-one             zepin-5-one                                            232. 8-chloro-4H-s-tria-                                                                             8-chloro-6-phenyl-4H-                                       zolo[4,3-a][1,5]- s-triazolo[4,3-a]-                                          benzodiazepin-5-one                                                                             [1,5]benzodiazepin-5-                                                         one                                                    233. 1-ethyl-8-chloro-4H-                                                                            1-ethyl-8-chloro-6-                                         s-triazolo[4,3-a]-                                                                              phenyl-4H-s-triazolo-                                       [1,5]benzodiazepin-                                                                             [4,3-a][1,5]benzodia-                                       5-one             zepin-5-one                                            234. 1-cyclopropyl-8-  1-cyclopropyl-8-chloro-                                     chloro-4H-s-triazolo-                                                                           6-phenyl-4H-s-triazolo-                                     [4,3-a][1,5]benzodia-                                                                           [4,3-a][1,5]benzodia-                                       zepin-5-one       zepin-5-one                                            235. 1-[(dimethylamino)-                                                                             1-[(dimethylamino)-                                         methyl]-8-chloro-4H-                                                                            methyl]-8-chloro-6-                                         s-triazolo[4,3-a]-                                                                              phenyl-4H-s-triazolo-                                       [1,5]benzodiazepin-                                                                             [4,3-a][1,5]benzodia-                                       5-one             zepin-5-one                                            ______________________________________                                    

EXAMPLE 2361-Methyl-8-chloro-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

To a stirred mixture of 12.4 g of1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one, 5 g ofcopper powder and 1 g of cupric sulfate in 100 ml ofo-chlorobromobenzene at 90° C., was added, portionwise over a 30 minuteperiod, 4.5 g of potassium acetate. The reaction is heated at 165° C.for 9 hours and then worked up as described in Example 29, Method C, togive the title compound.

EXAMPLES 237-243

Following the procedure of Example 236 but substituting the compoundsindicated in Column I below for1-methyl-8-chloro-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one inExample 236, the compounds indicated in Column II are obtained.

    ______________________________________                                        I                  II                                                         ______________________________________                                        237. 1-methyl-4H-s-triazolo-                                                                         1-methyl-6-(o-chloro-                                       [4,3-a][1,5]benzodia-                                                                           phenyl)-4H-s-triazolo-                                      zepin-5-one       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            238. 1-methyl-8-chloro-4H-                                                                           1-methyl-8-chloro-6-                                        s-triazolo[4,3-a][1,5]-                                                                         (o-chlorophenyl)-4H-                                        benzodiazepin-5-one                                                                             s-triazolo[4,3-a][1,5]-                                                       benzodiazepin-5-one                                    239. 1-methyl-8-methoxy-4H-                                                                          1-methyl-8-methoxy-6-                                       s-triazolo[4,3-a][1,5]-                                                                         (o-chlorophenyl)-4H-s-                                      benzodiazepin-5-one                                                                             triazolo[4,3-a][1,5]-                                                         benzodiazepin-5-one                                    240. 1-methyl-8-(trifluoro-                                                                          1-methyl-8-(trifluoro-                                      methyl)-4H-s-triazolo-                                                                          methyl)-6-(o-chloro-                                        [4,3-a][1,5]benzodia-                                                                           phenyl)-4H-s-triazolo-                                      zepin-5-one       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            241. 1-methyl-8-nitro-4H-                                                                            1-methyl-8-nitro-6-                                         s-triazolo[4,3-a]-                                                                              (o-chlorophenyl)-4H-                                        [1,5]benzodiazepin-                                                                             s-triazolo[4,3-a]-                                          5-one             [1,5]benzodiazepin-5-                                                         one                                                    242. 1-methyl-9-chloro-4H-                                                                           1-methyl-9-chloro-6-                                        s-triazolo[4,3-a]-                                                                              (o-chlorophenyl)-4H-s-                                      [1,5]benzodiazepin-                                                                             triazolo[4,3-a][1,5]-                                       5-one             benzodiazepin-5-one                                    243. 1-methyl-9-(trifluoro-                                                                          1-methyl-9-(trifluoro-                                      methyl)-4H-s-triazolo-                                                                          methyl)-6-(o-chloro-                                        [4,3-a][1,5]benzodia-                                                                           phenyl)-4H-s-triazolo-                                      zepin-5-one       [4,3-a][1,5]benzodia-                                                         zepin-5-one                                            244. 1,8-dimethyl-4H-s-                                                                              1,8-dimethyl-6-(o-chloro-                                   triazolo[4,3-a][1,5]-                                                                           phenyl)-4H-s-triazolo-                                      benzodiazepin-5-one                                                                             [4,3-a][1,5]benzodiaze-                                                       pin-5-one                                              ______________________________________                                    

EXAMPLE 245 N-Benzyl-N-(2'-nitro-5'-chlorophenyl)malonamic acid, ethylester

52 g of N-benzyl-N-(2-nitro-5-chlorophenyl) amine and 35.5 g of(chloroformyl)acetic acid ethyl ester in 500 ml benzene are refluxed for15 hours. The reaction is cooled, washed with dilute aqueous sodiumbicarbonate, dried and the solvent evaporated to give the titlecompound.

EXAMPLES 246-252

Following the procedure of Example 245, but substituting the compoundsindicated in Column I below for N-benzyl-N-(2-nitro-5-chlorophenyl)aminein Example 245, the compounds indicated in Column II are obatined.

    ______________________________________                                        I                  II                                                         ______________________________________                                        246. N-benzyl-N-[2-nitro-                                                                            N-benzyl-N-[2'-nitro-5'-                                    5-(trifluoromethyl)-                                                                            (trifluoromethyl)phenyl]-                                   phenyl amine      malonamic acid ethyl                                                          ester                                                  247. N-benzyl-N-(2-nitro-                                                                            N-benzyl-N-(2'-nitro-                                       5-methylphenyl)amine                                                                            5'-methylphenyl)malona-                                                       mic acid ethyl ester                                   248. N-benzyl-N-(2-nitro-                                                                            N-benzyl-N-(2'-nitro-                                       5-methoxyphenyl)amine                                                                           5'-methoxyphenyl)malona-                                                      mic acid ethyl ester                                   249. N-benzyl-N-(2-nitro-                                                                            N-benzyl-N-(2'-nitro-                                       phenyl)amine      phenyl)malonamic acid                                                         ethyl ester                                            250. N-benzyl-N-(2-nitro-                                                                            N-benzyl-N-(2'-nitro-                                       4-chlorophenyl)amine                                                                            4'-chlorophenyl)                                                              malonamic acid, ethyl                                                         ester                                                  251. N-(4-methoxybenzyl)-                                                                            N-(4-methoxybenzyl)-                                        N-(2-nitro-5-chloro-                                                                            N-(2'-nitro-5'-chloro-                                      phenyl)amine      phenyl)malonamic acid                                                         ethyl ester                                            252. N-(4-methoxybenzyl)-                                                                            N-(4-methoxybenzyl)-                                        N-( 2-nitro-5-(trifluoro-                                                                       N-[2'-nitro-5'-(tri-                                        methyl)phenyl]amine                                                                             fluoromethyl)phenyl]-                                                         malonamic acid, ethyl                                                         ester                                                  ______________________________________                                    

EXAMPLES 253-256

Following the procedure of Example 245 but substituting the compoundsindicated in column I below for (chloroformyl)acetic acid ethyl ester inexample 245, the compounds indicated in column II are obtained.

    ______________________________________                                        I                  II                                                         ______________________________________                                        253. (chloroformyl)acetic                                                                            N-benzyl-N-(2'-nitro-5'-                                    acid methyl ester chlorophenyl)malonamic                                                        acid methyl ester                                      254. (chloroformyl)acetic                                                                            N-benzyl-N-(2'-nitro-5'-                                    acid butyl ester  chlorophenyl)malonamic                                                        acid butyl ester                                       255. (chloroformyl)acetic                                                                            N-benzyl-N-(2'-nitro-5'-                                    acid phenyl ester chlorophenyl)malonamic                                                        acid phenyl ester                                      256. (chloroformyl)acetic                                                                            N-benzyl-N-(2'-nitro-5'-                                    acid (p-methylphenyl)                                                                           chlorophenyl)malonamic                                      ester             acid (p-methylphenyl)-                                                        ester                                                  ______________________________________                                    

EXAMPLE 257 N-Benzyl-N-(2'-amino-5'-chlorophenyl)malonamic acid ethylester

Method A

37.6 g of N-benzyl-N-(2'-nitro-5'-chlorophenyl)malonamic acid ethylester and 0.5 g 10% palladium-on-carbon in 200 ml ethanol containing 0.2moles of hydrogen chloride are hydrogenated on a Parr shaker, withcooling, at ambient temperature. The reaction is stopped after 0.3 molesof hydrogen are absorbed or when hydrogen uptake ceases, whichever comesfirst. The reaction is diluted with chloroform, filtered and thefiltrate evaporated. The residue is suspended in methylene chloride andshaken with excess aqueous sodium bicarbonate. The organic phase iswashed with water, dried and evaporated to give the title compound.

Method B

Following the procedure of Example 257, Method A, but substituting Raneynickel and methanol for the 10% palladium-on-carbon and ethanolichydrogen chloride, respectively, in Example 257, Method A, and runningthe reaction at an initial hydrogen pressure of 3 atm., gives the titlecompound.

EXAMPLES 258-268

Following the procedure of Example 257, Methods A and B, butsubstituting the compounds indicated in Column I below forN-benzyl-N-(2'-nitro-5'-chlorophenyl)malonamic acid ethyl ester inExample 257, Methods A and B, the compounds indicated in Column II areobtained.

    __________________________________________________________________________      I                II                                                         __________________________________________________________________________    258.                                                                             N-benzyl-N-[2'-nitro-                                                                       N-benzyl-N-[2'-amino-5'-                                        5'-(trifluoromethyl) phenyl]                                                                (trifluoromethyl)phenyl]                                        malonamic acid ethyl ester                                                                  malonamic acid ethyl                                                          ester                                                        259.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2'-amino-                                           5'-methylphenyl)                                                                            5'-methylphenyl)malona-                                         malonamic acid ethyl                                                                        mic acid ethyl ester                                            ester                                                                      260.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2'-amino-                                           5'-methoxyphenyl)                                                                           5'-methoxyphenyl)                                               malonamic acid ethyl                                                                        malonamic acid ethyl                                            ester         ester                                                        261.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2'-amino-                                           phenyl)malonamic acid,                                                                      phenyl)malonamic                                                ethyl ester   acid, ethyl ester                                            262.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2'-amino-                                           4'-chlorophenyl)                                                                            4'-chlorophenyl)                                                malonamic acid, ethyl                                                                       malonamic acid, ethyl                                           ester         ester                                                        263.                                                                             N-(4-methoxybenzyl)-                                                                        N-(4-methoxybenzyl)-                                            N-(2'-nitro-5'-chloro-                                                                      N-(2'-amino-5'-chloro-                                          phenyl)malonamic acid                                                                       phenyl)malonamic acid                                           ethyl ester   ethyl ester                                                  264.                                                                             N-(4-methoxybenzyl)-N-                                                                      N-(4-methoxybenzyl)-N-                                          [2'-nitro-5'-(trifluoro-                                                                    [2'-amino-5'-(trifluoro-                                        methyl)phenyl]malonamic                                                                     methyl)phenyl]malonamic                                         acid, ethyl ester                                                                           acid, ethyl ester                                            265.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2'-amino-                                           5'-chlorophenyl)malona-                                                                     5'-chlorophenyl)malonamic                                       mic acid methyl ester                                                                       acid methyl ester                                            266.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2'-amino-                                           5'-chlorophenyl)malona-                                                                     5'-chlorophenyl)malona-                                         mic acid butyl ester                                                                        mic acid butyl ester                                         267.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2' -amino-                                          5'-chlorophenyl)malona-                                                                     5'-chlorophenyl)malonamic                                       mic acid phenyl ester                                                                       acid phenyl ester                                            268.                                                                             N-benzyl-N-(2'-nitro-                                                                       N-benzyl-N-(2'-amino-                                           5'-chlorophenyl)malona-                                                                     5'-chlorophenyl)malona-                                         mic acid (p-methyl-                                                                         mic acid (p-methylphenyl)                                       phenyl)ester  ester                                                        __________________________________________________________________________

EXAMPLES 269-279

Following the procedure of Example 140, Methods B and D, butsubstituting the compounds indicated in Column I below forN-benzyl-N-(2'-amino-5'-chlorophenyl) malonamic acid, ethyl ester inExample 140, Methods B and D, the compounds indicated in Column II areobtained.

    ______________________________________                                        269. N-benzyl-N-[2'-amino-                                                                           7-(trifluoromethyl)-5-                                      5'-(trifluoromethyl)-                                                                           benzyl-1H-1,5-benzodia-                                     phenyl]malonamic  zepine-2,4-dione                                            acid ethyl ester                                                         270. N-benzyl-N-(2'-amino-                                                                           7-methyl-5-benzyl-1H-                                       5'-methylphenyl)  1,5-benzodiazepine-                                         malonamic acid    2,4-dione                                                   ethyl ester                                                              271. N-benzyl-N-(2'-amino-                                                                           7-methoxy-5-benzyl-1H-                                      5'-methoxyphenyl) 1,5-benzodiazepine-                                         malonamic acid    2,4-dione                                                   ethyl ester                                                              272. N-benzyl-N-(2'-amino-                                                                           5-benzyl-1H-1,5-benzodia-                                   phenyl)malonamic  zepine-2,4-dione                                            acid ethyl ester                                                         273. N-benzyl-N-(2'-amino-                                                                           8-chloro-5-benzyl-1H-                                       4'-chlorophenyl)malona-                                                                         1,5-benzodiazepine-2,4-                                     mic acid, ethyl ester                                                                           dione                                                  274. N-(4-methoxybenzyl)-                                                                            7-chloro-5-(p-methoxy-                                      N-(2'-amino-5'-chloro-                                                                          benzyl-1H-1,5-benzodia-                                     phenyl)malonamic acid                                                                           zepine-2,4-dione                                            ethyl ester                                                              275. N-(4'-methoxybenzyl)-N-                                                                         7-(trifluoromethyl)-5-                                      [2'-amino-5'-(trifluoro-                                                                        (p-methoxybenzyl)-1H-                                       methyl)phenyl]malonamic                                                                         1,5-benzodiazepine-2,4-                                     acid, ethyl ester dione                                                  276. N-benzyl-N-(2!-amino-                                                                           7-chloro-5-benzyl-1H-                                       5'-chlorophenyl)malona-                                                                         1,5-benzodiazepine-2,4-                                     mic acid methyl ester                                                                           dione                                                  277. N-benzyl-N-(2'-amino-                                                                           7-chloro-5-benzyl-1H-                                       5'-chlorophenyl)malona-                                                                         1,5-benzodiazepine-2,4-                                     mic acid butyl ester                                                                            dione                                                  278. N-benzyl-N-(2'-amino-                                                                           7-chloro-5-benzyl-1H-                                       5'-chlorophenyl)malona-                                                                         1,5-benzodiazepine-2,4-                                     mic acid phenyl ester                                                                           dione                                                  279. N-benzyl-N-(2'-amino-                                                                           7-chloro-5-benzyl-1H-                                       5'-chlorophenyl)malona-                                                                         1,5-benzodiazepine-2,4-                                     mic acid (p-methyl)-                                                                            dione                                                       phenyl)ester                                                             ______________________________________                                    

EXAMPLE 280 2,7-Dichloro-5-phenyl-3H-1,5-benzodiazepin-4-one

Method A

28.6 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione and 20.8 gof phosphorus pentachloride in 1000 ml of benzene is stirred for 10hours, then refluxed for 3 hours. The reaction is evaporated, azeotropedwith benzene and the solvent evaporated. The residue is stirred withcarbon tetrachloride and the title compound filtered off and dried.

Method B

To 28.6 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione and 24.2g of dimethylaniline in 200 ml of benzene is added 10.2 g of phosphorousoxychloride. The reaction mixture is refluxed for 14 hours under argon,cooled to 7° C., diluted with 100 ml of cold water and stirred for 0.25hour. The organic layer is separated, washed with 100 ml of cold water,dried and evaporated. The residue is stirred with 50 ml of carbontetrachloride and the title compound is filtered off and dried.

EXAMPLE 281 Acetic acid2-(7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one-2-yl)hydrazide

Method A

3.0 g of 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione and 1.8 gof acetic acid hydrazide in 100 ml ethanol is refluxed for 24 hours.During this time a slow stream of nitrogen is bubbled through thereaction mixture. The mixture is evaporated, the residue taken up inmethylene chloride, washed with water, dried and the solvent evaporated.The residue is chromatogtaphed on 10-1000μ silica gel plates (20×20 cm)with acetone-methanol (9:1) eluant. The band containing the product isremoved and stirred with acetone-methanol (4:1). The silica gel isfiltered off and the filtrate evaporated to give the title compound.

Method B

3.0 g of 2-hydrazino-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one and1.4 g of ethyl 1-acetoxyformate in 50 ml tetrahydrofuran containing onedrop of N-methylmorpholine is stirred at room temperature for 24 hours.The reaction mixture is evaporated to give the title compound. Furtherpurification is accomplished, if necessary, by chromatography asdescribed in Example 281, Method A.

EXAMPLE 282 2-Hydrazino-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one

Method A

3.8 g of2-[2(t-butoxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-oneand 1.78 g of hydrogen bromide in 200 ml methylene chloride is stirredfor 2 hours. The reaction mixture is washed with aqueous sodiumbicarbonate, water, dried and evaporated. The product is stirred withcarbon tetrachloride and the title compound is filtered off and dried.

Method B

4.32 g of2-[2-(benzyloxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-onein 400 ml 1,2-dimethoxy-ethane containing 0.4 g of 10%palladium-on-carbon is hydrogenated at 40 p.s.i. hydrogen pressure until0.01 moles of hydrogen are absorbed. The reaction is filtered, thefiltrate evaporated at room temperature and the residue stirred withcarbon tetrachloride to give the title compound.

EXAMPLE 2832-[2-(t-butoxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one

3.16 g of 2-(methylthio)-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-oneand 1.41 g of t-butylcarbazate in 60 ml of dimethyl formamide arerefluxed for 20 hours while a slow stream of nitrogen is bubbled throughthe reaction. The reaction is worked up as described in Example 29,Method A, to give the title compound.

EXAMPLE 2842-[2-(Benzyloxycarbonyl)hydrazino]-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one

Following the procedure of Example 283, but substituting benzylcarbazatefor t-butylcarbazate in Example 283, the title compound is obtained.

EXAMPLE 285 7-Amino-5-phenyl-1H-1,5-benzodiazepine-2,4-dione

29.7 g of 7-nitro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in 200 mlethanol containing 1.0 g of Raney nickel is hydrogenated at roomtemperature at an initial hydrogen pressure of 50 p.s.i. The reaction isstopped after 0.3 moles of hydrogen has been absorbed. The reactionmixture is filtered and the filtrate evaporated to give7-amino-5-phenyl-3H-1,5-benzodiazepine-2,4-dione.

EXAMPLE 286 7-Diazonium-5-phenyl-1H-1,5-benzodiazepin-4-one, sulfate

20 g of 7-amino-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in 100 ml ofacetic acid is added to a solution of 7.62 g of nitrosylsulfuric acid in10 ml of acetic acid at 0° C. After 30 minutes, 100 ml of ether isadded, with stirring and cooling, and the precipitated diazonium sulfateis filtered off and dried.

EXAMPLE 287 7-(Methylthio)-5-phenyl-1H-1,5-benzodiazepine-2,4-dione

3.76 g of 7-diazonium-5-phenyl-1H-1,5-benzodiazepine-2,4-dione sulfateis added portionwise with stirring under a dry-ice condenser, to asolution of 2.58 g of potassium methyl mercaptide in 100 ml of methylmercaptan. The reaction is gently refluxed for 24 hours. The reaction isevaporated; the residue diluted with 200 ml of methylene chloride,washed with a solution of 1.35 g acetic acid in 100 ml water, dried andevaporated to give the title compound. The product may be furtherpurified by chromatography on silica gel (e.g. 20-1000μ, 20×20 cmplates) using chloroform-ethyl acetate (6:4) as eluting solvent. Theband containing the title compound is removed, stirred with EtOAc-MeOH(9:1) and the silica gel is filtered off. The filtrate is evaporated togive the title compound.

EXAMPLE 2881-Methyl-8-(methylsulfinyl)-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

3.36 g of1-methyl-8-(methylthio)-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-oneand 2.14 g of sodium metaperiodate in 500 ml methanol is stirred at +5°C. for 24 hours. The reaction is evaporated; the residue dissolved inmethylene chloride, washed with water, dried and concentrated. Theconcentrate is chromatographed on silica gel (20-1000μ plates, 20×20 cm)using acetone-methanol (9:1) as eluting solvent. The band containing theproduct is removed, stirred with acetone-methanol (4:1) and the silicagel filtered off. The filtrate is evaporated to give the title compound.

EXAMPLE 2891-Methyl-8-amino-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

33.5 g of1-methyl-8-nitro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 100 ml of ethanol containing 2.0 g of Raney nickel is hydrogenated atroom temperature at an initial hydrogen pressure of 50 p.s.i. Thereaction is stopped when 0.3 moles of hydrogen has been absorbed; thesuspension is filtered and the filtrate evaporated to give the titlecompound.

EXAMPLE 2901-Methyl-8-acetamido-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

3.47 g of1-methyl-8-amino-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-oneand 1.02 g of acetic anhydride in 50 ml pyridine is stirred for 12 hoursthen refluxed for 30 minutes. The reaction is evaporated; the residue istaken up in chloroform, washed with dilute aqueous sodium bicarbonate,with water and dried. The solvent is evaporated to give the titlecompound.

EXAMPLE 2914-Hydroxy-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

44.6 g of4-(benzyloxy)-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 400 ml of ethanol containing 2.0 g of Raney nickel is hydrogenated atan initial hydrogen pressure of 40 p.s.i. After 0.1 mole of hydrogen hasbeen absorbed, the reaction is stopped, filtered and the solventevaporated. The residue is triturated in ether and the title compoundfiltered off and dried.

EXAMPLES 292-296

Following the procedure of Example 124, but substituting the compoundsindicated in column I below for diethylamine in example 124, thecompounds in column II are obtained.

    ______________________________________                                          I               II                                                          ______________________________________                                        292. 4-phenylpiperidine                                                                           1-(4-phenylpiperidinomethyl)-                                                 8-chloro-6-phenyl-4H-s-triazolo-                                              [4,3-a][1,5]benzodiazepin-5-one                           293. N-methylpiperazine                                                                           1-(4-methylpiperazinomethyl)-                                                 8-chloro-6-phenyl-4H-s-triazolo                                               [4,3-a][1,5]benzodiazepin-5-one                           294. N-(2-methoxyphenyl)-                                                                         1-[4-(2-methoxyphenyl)piperazino-                              piperazine     methyl]-8-chloro-6-phenyl-4H-                                                 s-triazolo[4,3-a][1,5]benzodiazepin-                                          5-one                                                     295. silver nitrite 1-(nitromethyl)-8-chloro-6-phenyl-                                            4H-s-triazolo[4,3-a][1,5]benzo-                                               diazepin-5-one                                            296. N-(t-butoxycarbonyl)-                                                                        1-[4-(4-butoxycarbonyl)-                                       piperazine     piperazinomethyl]-8-chloro-6-                                                 phenyl-4H-s-triazolo[4,3-a][1,5]-                                             benzodiazepin-5-one                                       ______________________________________                                    

EXAMPLE 2971-Piperazinomethyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

2 g. of1-[4-(t-butoxycarbonyl)-piperazinomethyl]-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 50 ml of trifluoroacetic acid is stirred for 2 hours. The reactionmixture is evaporated and the residue partitioned between methylenechloride and aqueous sodium bicarbonate. The organic phase is washedwith water, dried and evaporated to give the title compound.

EXAMPLE 2984-(3,4,5-trimethoxybenzoyloxy)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

Following the procedure of example 281, method B, but substituting ethyl1-(3,4,5-trimethoxybenzoyloxy)formate for ethyl 1-acetoxyformate and4-hydroxy-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onefor 2-hydrazino-7-chloro-5-phenyl-3H-1,5-benzodiazepin-4-one in example281, method B, the title compound is obtained.

EXAMPLE 2991-Methyl-8-chloro-6-(2',4'-dichlorophenyl)-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

Part A

20 g of 2',4',5-trichloro-2-nitrodiphenylamine in 100 ml of methanolcontaining 0.2 g of Raney nickel is hydrogenated at an initial hydrogenpressure of 7 atm. until three molar equivalents of hydrogen isconsumed. The suspension is filtered and the filtrate evaporated to givethe 2',4',5-trichloro-2-aminodiphenylamine.

Part B

Following the procedure of example 140, method A, but substituting theabove produced 2',4',5-trichloro-2-aminodiphenylamine for2-benzylamino-4-chloro-aniline in example 140, method A, gives7-chloro-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-2,4-dione.

Part C

Following the procedure of example 1 but substituting the above produced7-chloro-5-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-2,4-dione for7-chloro-5-phenyl-1H-1,5-benzodiazepine-2,4-dione in example 1, gives7-chloro-5-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-4-one-2-thione.

Part D

Following the procedure of example 29, method A, but substituting theabove produced7-chloro-5-(2',4'-dichlorophenyl)-1H-1,5-benzodiazepin-4-one-2-thionefor 7-chloro-5-phenyl-1H-1,5-benzodiazepin-4-one-2-thione in example 29,method A, gives the title compound of formula 1.

EXAMPLES 300-318

Following the procedure of parts A to D of the foregoing example butemploying as starting materials the substituted compound of formula 15where m is zero wherein the substituents and the position they occupyare indicated below:

    __________________________________________________________________________    Example                                                                       No.  3   4    5   6   2'   3'                                                                              4'   5'  6'                                      __________________________________________________________________________    300.     Cl   Cl                                                              301. Cl                                                                       302.     Cl                  CH.sub.3 SO.sub.2                                303.     CF.sub.3     Cl          CF.sub.3                                    304.          Cl      CH.sub.3                                                                             CH.sub.3                                         305.          Cl      CH.sub.3                                                                             Cl                                               306.          CH.sub.3 S     Cl                                               307.          Cl      Cl     CH.sub.3                                         308.     Cl       Cl                                                          309.     CH.sub.3 O                                                                         CH.sub.3 O                                                      310.     Cl   Cl           Cl                                                 311.     Cl           OCH.sub.3   OCH.sub.3                                   312.              Cl                                                          313.                  Cl   Cl                                                 314. CH.sub.3 O   CH.sub.3 O                                                  315.     Cl   CH.sub.3                                                        316.     CH.sub.3 SO.sub.2                                                    317.     Cl           CH.sub.3 S                                              318.     Cl           CH.sub.3 SO.sub.2                                       319.          Cl      F               F                                       __________________________________________________________________________

there is obtained the correspondingly substituted compound of formula Iwherein the substituents and the position they occupy are indicatedbelow:

    __________________________________________________________________________    Example                                                                       No.  7   8   9    10  2'   3'                                                                              4'   5'  6'                                      __________________________________________________________________________    300.     Cl  Cl                                                               301.              Cl                                                          302.         Cl              CH.sub.3 SO.sub.2                                303.         CF.sub.3 Cl          CF.sub.3                                    304.     Cl           CH.sub.3                                                                             CH.sub.3                                         305.     Cl           CH.sub.3                                                                             Cl                                               306.     CH.sub.3 S          Cl                                               307.     Cl           Cl     CH.sub.3                                         308. Cl      Cl                                                               309.     CH.sub.3 O                                                                        CH.sub.3 O                                                       310.     Cl  Cl              Cl                                               311.         Cl       OCH.sub.3   OCH.sub.3                                   312. Cl                                                                       313.                  Cl   Cl                                                 314. OCH.sub.3    OCH.sub.3                                                   315.     CH.sub.3                                                                          Cl                                                               316.         CH.sub.3 SO.sub.2                                                317.         Cl       SCH.sub.3                                               318.         Cl       CH.sub.3 SO.sub.2                                       319.     Cl           F               F                                       __________________________________________________________________________

EXAMPLE 3201-Methyl-8-(methylsulfonyl)-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

Following the procedure of example 288, but using 4.14 g instead of 2.14g of sodium metaperiodate, the title compound is obtained.

EXAMPLE 321 4-Chloro-2',6'-difluoro-2-nitrophenylamine

19.1 g of 2,4-dichloronitrobenzene and 126.0 g of 2,6-difluoroanilineand 16.4 g of sodium acetate are refluxed for 24 hours. After cooling,the reaction is poured into excess dilute hydrochloric acid, extractedwith ether and the ether is then dried and evaporated. The residue fromthe ether phase is chromatographed on neutral alumina with hexane-ether(9:1). The eluant is evaporated. The title compound is purified byrecrystallization from ethanol.

EXAMPLE 3221-Methyl-8-chloro-6-(5'-chloro-2'-nitrophenyl)-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

Following the procedure of parts B through D of example 299, butsubstituting 2-amino-5'-chloro-2'-nitrodiphenylamine for2',4',5-trichloro-2-aminodiphenylamine in part B, the title compound isobtained.

EXAMPLE 3231-Ethoxymethyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

Following the procedure of example 124, but substituting sodium ethoxideand ethanol for diethylamine in example 124, the title compound isobtained.

EXAMPLE 3244-(2-Dimethylaminoethyl)-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

37.0 g of1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-oneand 7.8 g of a 50 percent sodium hydride mineral oil dispersion in 400ml of dry 1,2-dimethoxyethane are stirred for 2 hours. A solution of13.7 g of 2-dimethylaminoethyl bromide in 40 ml of dry1,2-dimethoxyethane is added and the whole is stirred for 18 hours. Thesolvent is evaporated and the residue is partitioned between methylenechloride and water. The organic phase is washed with water, dried andevaporated to give the title compound.

EXAMPLES 325-338

Following the procedure of example 324 but substituting the compoundsindicated in column I below for 2-dimethylaminoethyl bromide in example324, the compounds indicated in column II are obtained:

    ______________________________________                                        I                II                                                           ______________________________________                                        325. 3-dimethylaminopropyl                                                                         4-(3-dimethylaminopropyl)-1-                                  chloride        methyl-8-chloro-6-phenyl-4H-2-                                                triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                              326. 2-pyrrolidinoethyl                                                                            4-(2-pyrrolidinoethyl)-1-                                     chloride        methyl-8-chloro-6-phenyl-4H-s-                                                triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                              327. 2-diethylaminoethyl                                                                           4-(2-diethylaminoethyl)-1-                                    bromide         methyl-8-chloro-6-phenyl-4H-s-                                                triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                              328. 2-morpholinoethyl                                                                             4-(2-morpholinoethyl)-1-methyl-                               chloride        8-chloro-6-phenyl-4H-s-triazolo-                                              [4,3-a][1,5]benzodiazepin-5-                                                  one                                                      329. 2-piperidinoethyl                                                                             4-(2-piperidinoethyl)-1-                                      chloride        methyl-8-chloro-6-phenyl-4H-s-                                                triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                              330. 2-(4-phenylpiperi-                                                                            4-[2-(4-phenylpiperidino)ethyl]-                              dino)ethyl chloride                                                                           1-methyl-8-chloro-6-phenyl-4H-s-                                              triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                              331. 2-piperazinoethyl                                                                             4-(2-piperazinoethyl)-1-methyl-                               chloride        8-chloro-6-phenyl-4H-s-                                                       triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                              332. 2-(4-           4-[2-(4-methylpiperazino)ethyl]-                              methylpiperazino)-                                                                            1-methyl-8-chloro-6-phenyl-4H-s-                              ethyl chloride  triazolo[4,3-a][1,5]benzodia-                                                 zepin-5-one                                              333. 2-(4-           4-[2-(4-phenylpiperazino)ethyl]-                              phenylpiperazino)-                                                                            1-methyl-8-chloro-6-phenyl-4H-s-                              ethyl chloride  triazolo[4,3-a][1,5]benzodiazepin-                                            5-one                                                    334. 3-[4-           4-[3-[4-(2-methoxyphenyl)pipera-                              (2-methoxyphenyl)-                                                                            zino[propyl]-1-methyl-8-chloro-                               piperazino]propyl-                                                                            6-phenyl-4H-s-triazolo[4,3,-a]-                               chloride        [1,5]benzodiazepin-5-one                                 335. 3-piperidinopropyl                                                                            4-(3-piperidinopropyl)-1-methyl-                              chloride        8-chloro-6-phenyl-4H-s-triazolo-                                              [4,3-a]]1,5]benzodiazepin-5-one                          336. 3-(4-methylpipera-                                                                            4-[ 3-(4-methylpiperazino)propyl]-                            zino)propyl chloride                                                                          1-methyl-8-chloro-6-phenyl-4H-                                                s-triazolo[4,3-a][1,5]benzodia-                                               zepin-5-one                                              337. 2-(N-benzyl-N-  4-[2-(N-benzyl-N-                                             methylamino)ethyl                                                                             methylamino)ethyl]-                                           chloride        1-methyl-8-chloro-6-phenyl-4H-                                                s-triazolo[4,3-a][1,5]benzodia-                                               zepin-5-one                                              338. 3-[(5-butoxycarbonyl)-                                                                        4-[3-[(5-butoxycarbonyl)amino]-                               amino]propyl chloride                                                                         propyl]-1-methyl-8-chloro-6-                                                  phenyl-4H-s-triazolo[4,3-a][1,5]-                                             benzodiazepin-5-one                                      ______________________________________                                    

EXAMPLE 3394-(2-Methylaminoethyl)-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

4 g of4-[2-(N-benzyl-N-methylamino)ethyl]-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 100 ml of ethanol containing 0.4 of Raney nickel is hydrogenated at50 p.s.i. hydrogen pressure until 0.0085 moles of hydrogen is absorbed.The suspension is filtered and the filtrate is evaporated. The residueis triturated with a small amount of cold ether and the title compoundis filtered off and dried.

EXAMPLE 3404-(3-aminopropyl)-1-methyl-8-dichloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one

2.5 g of4-[2-(N-t-butoxycarbonylamino)propyl]-1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-onein 50 ml of trifluoroacetic acid is stirred at room temperature for 2hours. The reaction is evaporated and the residue is stirred with asolution of 1.9 g of sodium bicarbonate in 400 ml of methanol-water(10:1). After 3 hours the reaction is evaporated and the residue ispartitioned between methylene chloride and water. The methylene chlorideis washed with water, dried and evaporated to give the title compound.

EXAMPLES 341-343

Following the procedure of example 29, Method A, but substituting thecompounds indicated in column I below for acetic acid hydrazide inexample 29, Method A, the compounds indicated in column II are obtained.

    ______________________________________                                        I                 II                                                          ______________________________________                                        341. picolinic acid hydrazide                                                                       1-(2-pyridyl)-8-chloro-6-phenyl-                                              4H-s-triazolo[4,3-a][1,5]benzo-                                               diazepin-5-one                                          342. nicotinic acid hydrazide                                                                       1-(3-pyridyl)-8-chloro-6-phenyl-                                              4H-s-triazolo[4,3-a][1,5]benzo-                                               diazepin-5-one                                          343. isonicotinic acid                                                                              1-(4-pyridyl)-8-chloro-6-phenyl-                             hydrazide        4H-s-triazolo[4,3-a][1,5]benzo-                                               diazepin-5-one                                          343. m-(trifluoromethyl)benzoic                                                                     1-[3-(trifluoromethyl)phenyl]-8-                             acid hydrazide   chloro-6-phenyl-4H-s-triazolo-                                                [4,3-a][1,5]benzodiazepin-5-one                         344. o-chlorobenzoic acid                                                                           1-(2-chlorophenyl)-8-chloro-                                 hydrazide        6-phenyl-4H-s-triazolo[                                                       4,3-a][1,5]-                                                                  benzodiazepin-5-one                                     345. p-methylbenzoic acid                                                                           1-(4-methylphenyl)-8-chloro-6-                               hydrazide        phenyl-4H-s-triazolo[4,3-a][1,5]-                                             benzodiazepin-5-one                                     346. m-methoxybenzoic acid                                                                          1-(3-methoxyphenyl)-8-chloro-6-                              hydrazide        phenyl-4H-s-triazolo[4,3-a][1,5]-                                             benzodiazepin-5-one                                     347. m-nitrobenzoic acid                                                                            1-(3-nitrophenyl)-8-chloro-6-                                hydrazide        phenyl-4H-s-triazolo[4,3-a][1,5]-                                             benzodiazepin-5-one                                     348. p-acetamidobenzoic                                                                             1-(4-acetamidophenyl)-8-                                                      chloro-6-                                                    acid hydrazide   phenyl-4H-s-triazolo[4,3-a][1,5]-                                             benzodiazepin-5-one                                     349. o-(methylthio)benzoic                                                                          1-[2-(methylthio)phenyl]-8-                                                   chloro-                                                                       6-phenyl-4H-s-triazolo[4,3-a][1,5]-                                           benzodiazepin-5-one                                     350. p-(methylsulfonyl)-                                                                            1-[4-(methylsulfonyl)phenyl]-8-                              benzoic acid hydrazide                                                                         chloro-6-phenyl-4H-s-triazolo-                                                [4,3-a][1,5]benzodiazepin-5-one                         ______________________________________                                    

EXAMPLE 351

A group of experimental animals composed of rats, mice and monkeys areorally administered1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one.The compound is administered at the following dosage levels: rats, 3.1mg/kg; mice, 1 mg/kg; monkeys, 2.5 mg/kg. Ataxia is produced in all ofthe animals of the test group at the dosage levels indicated.

EXAMPLE 352

A group of rats is orally administered1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one.The group is then subjected to the conflict test procedure described byVogel et al., Psychopharmacologist, 21, 1 (1970). A tranquilizing effectis produced in all of the test animals.

EXAMPLE 353

A group of mice is orally administered1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-oneat a dosage level of 12 mg/kg. At this dosage level the convulsanteffect of 135 mg of subcutaneously administered pentylenetetrazole isantagonized in 50% of the animals.

EXAMPLE 354

In another test, the same group of mice is orally administered 26 mg/kgof the foregoing compound. This dosage level antagonizes the convulsanteffect of 75 mg of intravenously administered strychnine in 50% of thetest animals.

EXAMPLE 355

A group of mice are orally administered 30 mg/kg of1-methyl-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,5]benzodiazepin-5-one.Food consumption is increased in the test animals by 100% compared to agroup of control animals.

EXAMPLE 356

    ______________________________________                                        Preparation of capsule formulation                                            Ingredient           Milligrams per Capsule                                   ______________________________________                                        1-Methyl-8-chloro-6-phenyl-4H-s-                                              triazolo[4,3-a][1,5]benzodiazepin-5-one                                                            400                                                      Starch               80                                                       Magnesium stearate   5                                                        ______________________________________                                    

The active ingredient, starch and magnesium stearate are blendedtogether. The mixture is used to fill hard shell capsules of a suitablesize at a fill weight of 485 milligrams per capsule.

EXAMPLE 357

    ______________________________________                                        Preparation of tablet formulation                                             Ingredient           Milligrams per Tablet                                    ______________________________________                                        1-Methyl-8-chloro-6-phenyl-4H-s-                                              triazolo[4,3-a][1,5]benzodiazepin-5-one                                                            300                                                      Lactose              200                                                      Corn starch (for mix)                                                                              50                                                       Corn starch (for paste)                                                                            50                                                       Magnesium stearate   6                                                        ______________________________________                                    

The active ingredient, lactose and corn starch (for mix) are blendedtogether. The corn starch (for paste) is suspended in water at a ratioof 10 grams of corn starch per 80 milliliters of water and heated withstirring to form a paste. This paste is then used to granulate the mixedpowders. The wet granules are passed through a No. 8 screen and dried at120° F. The dry granules are passed through a No. 16 screen. The mixtureis lubricated with magnesium stearate and compressed into tablets in asuitable tableting machine. Each tablet contains 300 milligrams ofactive ingredient.

EXAMPLE 358

    ______________________________________                                        Preparation of oral syrup formulation                                         Ingredient               Amount                                               ______________________________________                                        1-Methyl-8-chloro-6-phenyl-4H-s-                                              triazolo[4,3-a][1,5]benzodiazepin-5-one                                                                500 mg.                                              Sorbitol solution (70% N.F.)                                                                            40 ml.                                              Sodium benzoate          150 mg.                                              Sucaryl                   90 mg.                                              Saccharin                 10 mg.                                              Red Dye (F.D. & Co. No. 2)                                                                              10 mg.                                              Cherry flavor             50 mg.                                              Distilled water     qs to    100 ml.                                          ______________________________________                                    

The sorbitol solution is added to 40 milliliters of distilled water andthe active ingredient is suspended therein. The sucaryl, saccharin,sodium benzoate, flavor and dye are added and dissolved in the abovesolution. The volume is adjusted to 100 milliliters with distilledwater.

Other ingredients may replace those listed in the above formulation. Forexample, a suspending agent such as bentonite magma, tragacanth,carboxymethylcellulose, or methylcellulose may be used. Phosphates,citrates or tartrates may be added as buffers. Preservatives may includethe parabens, sorbic acid and the like and other flavors and dyes may beused in place of those listed above.

What is claimed is:
 1. A compound of the formula ##STR30## wherein R² isH; alkyl of 1-4 carbons optionally substituted by amino, mono-loweralkyl amino, di-lower alkyl amino, cyclic imines of formula ##STR31##where D is methylene, oxygen or N--R¹⁰ and where p and q are the same ordifferent and are the integers 1, 2, and 3 provided that p+q is at least1; hydroxy; alkoxy of 1-6 carbons or ##STR32## where R⁵ is alkyl of 1-5carbons optionally substituted by phenyl or X-substituted phenyl; or R⁵is phenyl optionally substituted by 1 or more X-substituents; R¹⁰ ishydrogen, alkyl of 1-4 carbons or phenyl optionally substituted by X, Vis hydrogen, ##STR33## X and Y are the same or different and arehydrogen, F, Cl, Br, trifluoromethyl, alkyl of from 1-6 carbons, alkoxyof from 1-6 carbons, nitro, cyano, amino, alkanoylamino of 1-4 carbons,alkylthio of 1-6 carbons, alkylsulfinyl of 1-6 carbons or alkyl sulfonylof 1-6 carbons; n is 0, 1 or 2; and when V is hydrogen or ##STR34## U isH; phenyl; X-substituted phenyl wherein X is as defined below; 2, 3- or4-pyridyl, or cycloalkyl of 3-5 carbons; alkyl of 1 to 4 carbons orphenyl-alkyl, and when V is ##STR35## U is alkyl of from 1 to 4 carbonssubstituted by the groups, ##STR36## where P and Q are the same ordifferent and are hydrogen, phenyl, X-substituted phenyl, naphthyl orX-substituted naphthyl, with the proviso that at least one of P and Q isone of the foregoing aryl radicals, and R¹¹ is hydrogen or alkyl of from1 to 4 carbons.
 2. A compound according to claim 1 wherein U iscycloalkyl of 3-5 carbons.
 3. A compound according to claim 1 wherein Uis phenyl or pyridyl, R² is hydrogen, X_(n) is hydrogen, chloro,trifluoromethyl, thiomethyl or nitro, each of the foregoing being in the8-position and Y_(n) is fluoro or chloro in the 2'-position, or Y_(n) isdifluoro in the 2'- and 6'-positions.
 4. A compound according to claim 1wherein R² is hydrogen, methyl, dimethylaminomethyl ordiethylaminomethyl.
 5. A compound according to claim 4 wherein U isphenyl or pyridyl, R² is hydrogen, methyl, dimethylaminomethyl, ordiethylaminomethyl, X_(n) is chloro in the 8-position and Y_(n) isfluoro or chloro in the 2'-position or difluoro in the 2'-position and6'-positions.